Study to Evaluate the Efficacy and Safety of Glycopyrronium or Indacaterol Maleate and Glycopyrronium Bromide Fixed-dose Combination Regarding Symptoms and Health Status in Patients With Moderate COPD Switching From Treatment With Any Standard COPD Regimen
Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT01985334
Collaborator
(none)
4,389
544
8
26.4
8.1
0.3
Study Details
Study Description
Brief Summary
The main goal of this study is to evaluate the efficacy and safety of glycopyrronium bromide and indacaterol maleate and glycopyrronium bromide fixed dose combination (FDC) in patients with moderate COPD who switch from their current COPD therapy. This study aims to provide data on how non-exacerbating, but still symptomatic patients with moderate COPD switching from their current COPD treatment to glycopyrronium bromide or indacaterol maleate and glycopyrronium bromide FDC maintain or improve their symptoms. Another purpose of this study is to increase awareness and usage of validated COPD symptoms tools and dyspnea questionnaires in order to facilitate clinical assessment and improve early diagnosis of symptomatic patients.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Detailed Description
The treatment epoch will last 12 weeks. The total duration of the study for each patient is 12 weeks (from randomization) plus 30 days of safety follow-up.
The study has three phases: screening phase (=wash-out period, if required), treatment phase and safety follow-up phase.
Eligible patients will be randomized to either receive glycopyrronium or indacaterol maleate and glycopyrronium bromide fixed dose combination or to remain in their baseline therapy, in an allocation ratio of 3:1 for each cluster (Groups A, B, C, and D), based on their COPD symptoms and baseline treatment:
Group A: Patients treated with any SABA ( Short-acting β2-adrenergic agonist) and/or SAMA (Short-acting muscarinic antagonist) as monotherapy or in free or fixed dose combination (FDC) will be assigned to glycopyrronium or will remain in their baseline therapy (3:1) Group B: Patients treated with any LABA (Long-acting β2-adrenergic agonist) or LAMA (Long-acting muscarinic antagonist) monotherapy and mMRC score =1 point will be assigned to glycopyrronium or will remain in their baseline therapy (3:1) Group C: Patients treated with any LABA and ICS (Inhaled corticosteroid) in free or FDC will be assigned to indacaterol maleate and glycopyrronium bromide fixed dose combination or will remain in their baseline therapy (3:1) Group D: Patients treated with any LABA or LAMA monotherapy and mMRC score >1 point will be assigned to indacaterol maleate and glycopyrronium bromide fixed dose combination or will remain in their baseline therapy (3:1) Due to low recruitment in Groups A and B that would lead to a significant delay of trial completion, a protocol amendment was made in order to close the recruitment of Groups A and B at the time the randomization in Groups C and D would be completed. Recruitment of the Groups C and D continued as originally planned
Study Design
Study Type:
Interventional
Actual Enrollment
:
4389 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Prospective, Multicenter, 12-week, Randomized Open-label Study to Evaluate the Efficacy and Safety of Glycopyrronium (50 Micrograms o.d.) or Indacaterol Maleate and Glycopyrronium Bromide Fixed-dose Combination (110/50 Micrograms o.d.) Regarding Symptoms and Health Status in Patients With Moderate Chronic Obstructive Pulmonary Disease (COPD) Switching From Treatment With Any Standard COPD Regimen
Actual Study Start Date
:
Feb 14, 2014
Actual Primary Completion Date
:
Apr 29, 2016
Actual Study Completion Date
:
Apr 29, 2016
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: A1 (any SABA and/or SAMA) Patients treated with any SABA and/or SAMA as monotherapy or in free or fixed dose combination will be assigned to glycopyrronium or will remain in their baseline therapy (3:1) during 90 days of treatment |
Drug: Glycopyrronium
Glycopyrronium 50 µg capsule for inhalation via SDDPI once per day
Other Names:
Drug: SABA
Short-acting β2-adrenergic agonist (SABA) as per approved by each country and as prescribed for each patient, used as background therapy
Drug: SAMA
Short-acting muscarinic antagonist (SAMA) as per approved by each country and as prescribed for each patient, used as background therapy
|
| Experimental: A2 (glycopyrronium) Patients treated with any SABA and/or SAMA as monotherapy or in free or FDC at enrollment and randomized to switch in treatment with glycopyrronium (50 μg o.d.) |
Drug: Glycopyrronium
Glycopyrronium 50 µg capsule for inhalation via SDDPI once per day
Other Names:
Drug: SABA
Short-acting β2-adrenergic agonist (SABA) as per approved by each country and as prescribed for each patient, used as background therapy
Drug: LABA
Long Acting Beta Agonist (LABA) as per approved by each country and as prescribed for each patient, used as background therapy
Drug: SAMA
Short-acting muscarinic antagonist (SAMA) as per approved by each country and as prescribed for each patient, used as background therapy
|
| Experimental: B1 (any LAMA or LABA and mMRC=1) Patients treated with any LABA or LAMA monotherapy and mMRC score =1 point at Visit 1 and randomized to remain in their baseline treatment with LABA or LAMA |
Drug: LABA
Long Acting Beta Agonist (LABA) as per approved by each country and as prescribed for each patient, used as background therapy
Drug: Indacaterol maleate and glycopyrronium bromide
Indacaterol maleate and glycopyrronium bromide fixed dose combination (110/50 µg) capsule for inhalation via SDDPI, once a day
Drug: LAMA
Long Acting Muscarinic Antagonist (LAMA) as per approved by each country and as prescribed for each patient, used as background therapy
Drug: ICS
Inhaled corticosteroid (ICS) as per approved by each country and as prescribed for each patient, used as background therapy
|
| Experimental: B2 (glycopyrronium and mMRC=1) Patients treated with any LABA or LAMA monotherapy and mMRC score =1 point at Visit 1 and randomized to switch in treatment with glycopyrronium (50 μg o.d.) |
Drug: LABA
Long Acting Beta Agonist (LABA) as per approved by each country and as prescribed for each patient, used as background therapy
Drug: Indacaterol maleate and glycopyrronium bromide
Indacaterol maleate and glycopyrronium bromide fixed dose combination (110/50 µg) capsule for inhalation via SDDPI, once a day
Drug: LAMA
Long Acting Muscarinic Antagonist (LAMA) as per approved by each country and as prescribed for each patient, used as background therapy
|
| Experimental: C1 (any LABA and ICS) Patients treated with any LABA and ICS in free or FDC at enrollment and randomized to remain in their baseline treatment with LABA and ICS in free or FDC |
Drug: LABA
Long Acting Beta Agonist (LABA) as per approved by each country and as prescribed for each patient, used as background therapy
Drug: ICS
Inhaled corticosteroid (ICS) as per approved by each country and as prescribed for each patient, used as background therapy
|
| Experimental: C2 (indacaterol/glycopyrronium) Patients treated with any LABA and ICS in free or FDC at enrollment and randomized to switch in treatment with indacaterol maleate and glycopyrronium bromide FDC (110/50 μg o.d.) |
Drug: LABA
Long Acting Beta Agonist (LABA) as per approved by each country and as prescribed for each patient, used as background therapy
Drug: ICS
Inhaled corticosteroid (ICS) as per approved by each country and as prescribed for each patient, used as background therapy
|
| Experimental: D1 (any LAMA or LABA and mMRC>1) Patients treated with any LABA or LAMA monotherapy and mMRC score >1 point at Visit 1 and randomized to remain their baseline in treatment with LABA or LAMA |
Drug: LAMA
Long Acting Muscarinic Antagonist (LAMA) as per approved by each country and as prescribed for each patient, used as background therapy
|
| Experimental: D2 (indacaterol/glycopyrronium and mMRC>1) Patients treated with any LABA or LAMA monotherapy and mMRC score >1 point at Visit 1 and randomized to switch in treatment with indacaterol maleate and glycopyrronium bromide FDC (110/50 μg o.d.). |
Drug: LAMA
Long Acting Muscarinic Antagonist (LAMA) as per approved by each country and as prescribed for each patient, used as background therapy
|
Outcome Measures
Primary Outcome Measures
- Trough FEV1 at Week 12 for Group: Glycopyrronium vs. Short-acting Bronchodilators (SABA and/or SAMA as Monotherapy or in Free or FDC) [Week 12 (Visit 4)]
Trough FEV1 at visit 4 is defined as FEV1, computed as the mean of forced expiratory volume in 1 second 15min and 45 min pre dose measurements, at the end of the dosing interval
- Trough FEV1 at Week 12 for Group: Glycopyrronium vs. Long-acting Bronchodilators (LABA or LAMA Monotherapy) [Week 12 (Visit 4)]
Trough FEV1 at visit 4 is defined as FEV1, computed as the mean of forced expiratory volume in 1 second 15min and 45 min pre dose measurements, at the end of the dosing interval
- Trough FEV1 at Week 12 for Group: Indacaterol Maleate and Glycopyrronium Bromide FDC vs. LABA and ICS in Free or FDC [Week 12 (Visit 4)]
Trough FEV1 at visit 4 is defined as FEV1, computed as the mean of forced expiratory volume in 1 second 15min and 45 min pre dose measurements, at the end of the dosing interval.
- Trough FEV1 at Week 12 for Group: Indacaterol Maleate and Glycopyrronium Bromide FDC vs. Long-acting Bronchodilators (LABA or LAMA Monotherapy) [Week 12 (Visit 4)]
Trough FEV1 at visit 4 is defined as FEV1, computed as the mean of forced expiratory volume in 1 second 15min and 45 min pre dose measurements, at the end of the dosing interval.
- Change From Baseline on Transition Dyspnea Index (TDI) for Groups: Glycopyrronium vs. Short-acting Bronchodilators (SABA and/or SAMA as Monotherapy or in Free or FDC) [Day 1 (baseline) and week 12]
Transition Dyspnea Index (TDI) captures changes from baseline. The TDI score is based on three domains with each domain scored from -3 (major deterioration) to +3 (major improvement), to give an overall score of -9 to +9, a negative score indicating a deterioration from baseline. A TDI focal score of 1 is considered to be a clinically significant improvement from baseline.
- Change From Baseline on Transition Dyspnea Index (TDI) for Groups: Glycopyrronium vs. Long-acting Bronchodilators (LABA or LAMA Monotherapy) [Day 1 (baseline) and week 12]
Transition Dyspnea Index (TDI) captures changes from baseline. The TDI score is based on three domains with each domain scored from -3 (major deterioration) to +3 (major improvement), to give an overall score of -9 to +9, a negative score indicating a deterioration from baseline. A TDI focal score of 1 is considered to be a clinically significant improvement from baseline.
- Change From Baseline on Transition Dyspnea Index (TDI) for Groups: Indacaterol Maleate and Glycopyrronium Bromide FDC vs. LABA and ICS in Free or FDC [Day 1 (baseline) and week 12]
Transition Dyspnea Index (TDI) captures changes from baseline. The TDI score is based on three domains with each domain scored from -3 (major deterioration) to +3 (major improvement), to give an overall score of -9 to +9, a negative score indicating a deterioration from baseline. A TDI focal score of 1 is considered to be a clinically significant improvement from baseline.
- Change From Baseline on Transition Dyspnea Index (TDI) for Groups: Indacaterol Maleate and Glycopyrronium Bromide FDC vs. Long-acting Bronchodilators (LABA or LAMA Monotherapy) [Day 1 (baseline) and week 12]
Transition Dyspnea Index (TDI) captures changes from baseline. The TDI score is based on three domains with each domain scored from -3 (major deterioration) to +3 (major improvement), to give an overall score of -9 to +9, a negative score indicating a deterioration from baseline. A TDI focal score of 1 is considered to be a clinically significant improvement from baseline.
Secondary Outcome Measures
- Trough FEV1 at Week 12 for Group: Glycopyrronium vs. Short-acting Bronchodilators (SABA and/or SAMA as Monotherapy or in Free or FDC) or vs. Long-acting Bronchodilators (LABA or LAMA Monotherapy) [12 Weeks]
Trough FEV1 at visit 4 is defined as FEV1, computed as the mean of forced expiratory volume in 1 second 15min and 45 min pre dose measurements, at the end of the dosing interval
- Change From Baseline on on Transition Dyspnea Index (TDI) for Groups: Glycopyrronium vs. Short-acting Bronchodilators (SABA and/or SAMA as Monotherapy or in Free or FDC) or Long-acting Bronchodilators (LABA or LAMA Monotherapy) [Day 1 (baseline) and week 12]
Transition Dyspnea Index (TDI) captures changes from baseline. The TDI score is based on three domains with each domain scored from -3 (major deterioration) to +3 (major improvement), to give an overall score of -9 to +9, a negative score indicating a deterioration from baseline. A TDI focal score of 1 is considered to be a clinically significant improvement from baseline.
- Trough FEV1 at Week 12 for Group: Indacaterol Maleate and Glycopyrronium Bromide FDC vs. LABA or LAMA Monotherapy or LABA and ICS in Free or FDC on Trough FEV1 at Week 12. [12 Weeks]
Trough FEV1 at visit 4 is defined as FEV1, computed as the mean of forced expiratory volume in 1 second 15min and 45 min pre dose measurements, at the end of the dosing interval.
- Change From Baseline on Transition Dyspnea Index (TDI) for Groups: Indacaterol Maleate and Glycopyrronium Bromide FDC vs. LABA or LAMA Monotherapy or LABA and ICS in Free or FDC [Day 1 (baseline) and week 12]
Transition Dyspnea Index (TDI) captures changes from baseline. The TDI score is based on three domains with each domain scored from -3 (major deterioration) to +3 (major improvement), to give an overall score of -9 to +9, a negative score indicating a deterioration from baseline. A TDI focal score of 1 is considered to be a clinically significant improvement from baseline.
- Change From Baseline on Total Score of COPD Assessment Test (CAT) for Groups: Glycopyrronium and Indacaterol Maleate and Glycopyrronium Bromide FDC [Day 1 (baseline) and Week 12]
Total score of COPD Assessment Test (CAT) will be measured at baseline and at week 12. This questionnaire is completed by the patient. The score ranges from 0-40 where higher scores represent worse health status. CAT scores ≥ 10 are associated with significantly impaired health status.
- Change From Baseline on Total Score of Clinical COPD Questionnaire (CCQ) for Groups: Glycopyrronium and Indacaterol Maleate and Glycopyrronium Bromide FDC [Day 1 (baseline) and Week 12]
The Clinical COPD Questionnaire (CCQ) is a self-administered 10-item questionnaire developed to measure clinical control in patients with COPD. Patients will be instructed to recall their experiences during the previous week. They respond to each question using a 7-point scale from 0 = asymptomatic/no imitation to 6 = extremely symptomatic/totally limited. The questionnaire is divided into 3 domains (symptoms [items 1, 2, 5, and 6] functional [items 7, 8, 9, and 10] and mental state [items 3 and 4]). The overall clinical COPD control score and the scores of the domains are calculated by adding all the scores together and dividing this sum by the number of questions. Thus, the overall clinical COPD control score as well as the score on each of the three domains varies between 0 (very good control) to 6 (extremely poor control).
- Mean Number of Puffs of Rescue Medication Use for Groups: Glycopyrronium and Indacaterol Maleate and Glycopyrronium Bromide FDC [12 weeks]
Mean number of puffs of rescue medication use will be measured using eDiary data over 12 weeks of treatment.
- Mean Change From Baseline Reported Symptoms of COPD for Groups: Glycopyrronium and Indacaterol Maleate and Glycopyrronium Bromide FDC [Baseline, 12 weeks]
Patient-reported symptoms of COPD combined will be measured using eDiary data reported over the 12 week treatment period. The mean total symptom scores and mean individual symptom scores for the patient were calculated for the whole study period. The mean change from baseline in the total scores and in the individual scores were summarized by treatment and were analyzed for the percentage of nights with no nighttime awakenings and percentage of days with no symptoms.
Eligibility Criteria
Criteria
Ages Eligible for Study:
40 Years
to 95 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Male and female adults aged ≥ 40 years
-
Patients with moderate COPD according to the GOLD criteria 2013
-
Current or ex-smokers who have a smoking history of at least 10 pack years
-
Patients with airflow limitation indicated by a postbronchodilator FEV1 ≥50% and <80% of the predicted normal value and a post-bronchodilator FEV1/FVC <0.7 at Visit 2. Post- bronchodilator refers to within 10-15 min of inhalation of 400 μg (4x100 μg) of salbutamol
-
Patients who, at Visit 1, have been for at least 3 months on a stable dose of one of the following COPD baseline treatments: *Any SABA monotherapy (such as, but not limited to, salbutamol) *Any SAMA monotherapy (such as, but not limited to, ipratropium) *Any SABA and SAMA in free or FDC (such as, but not limited to, salbutamol/ipratropium) *Any LABA monotherapy (such as, but not limited to, formoterol, salmeterol, indacaterol) *Any LAMA monotherapy (such as, but not limited to, tiotropium, aclidinium) except glycopyrronium bromide (NVA237) *Any LABA and ICS in free (ICS such as, but not limited to, beclomethasone, fluticasone) or FDC (such as, but not limited to, salmeterol/fluticasone, formoterol/budesonide).
-
Patients with an mMRC score ≥1 at Visit 1.
Exclusion Criteria:
-
Patients with conditions contraindicated for treatment with, or having a history of reactions/ hypersensitivity to any of the following inhaled drugs or to drugs of similar chemical classes or any component thereof: Anti-cholinergic agents, Long- and short-acting 2-adrenergic agonists, Sympathomimetic amines, Lactose or any of the other excipients of the trial medication.
-
Patients with narrow-angle glaucoma or urinary retention, severe renal impairment (history of estimated glomerular filtration rate below 30 ml/min/1.73 m2 within 12 months prior to visit 1), including those with end-stage renal disease requiring dialysis.
-
Patients with active/ clinical history of asthma.If the Investigator finds clear and compelling evidence that a patient was misdiagnosed with asthma in the past, then the burden of proof is on the Investigator to properly document this previous misdiagnosis. This documentation must include the rationale for this change in diagnosis including reference to the differential diagnosis that supports this decision.
-
Patients with a history of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
-
Patients who have a post-bronchodilator FEV1 decrease more than 10% compared to pre-bronchodilator FEV1 result at Visit 2 (see Appendix 5 for details).
-
A documented history of >1 COPD exacerbation requiring treatment with systemic corticosteroids or antibiotics and/or hospitalization in the previous 12 months.
-
Patients who have NOT had a COPD exacerbation in the previous 12 months and develop a COPD exacerbation between screening (Visit 1) and (Visit 2) will not be eligible but will be permitted to be re-screened after a minimum of 6 weeks after the resolution of the COPD exacerbation. (Patients suffering an exacerbation between Visit 1 and Visit 2 can only be re-screened in case it is the first one in the previous 12 months. In case this COPD exacerbation has led to an alteration of the patient COPD treatment, before this patient can be re-screened 3 months of stable COPD treatment will be required as described in Inclusion Criterion 6).
-
Patients who, in the judgment of the investigator, have a clinically relevant laboratory abnormality or a clinically significant condition such as (but not limited to): *Unstable ischemic heart disease, left ventricular failure (NYHA Class III & IV), history of myocardial infarction,arrhythmia (excluding chronic stable atrial fibrillation). Patients with such events not considered clinically significant by the investigator may be considered for inclusion in the study.*Uncontrolled hypo-or hyperthyroidism, hypokalaemia or hyperadrenergic state. *Any condition which might compromise patient safety or compliance, interfere with evaluation, or preclude completion of the study
-
History of resting QTc (Fridericia preferred, but Bazett acceptable) >450 msec (male) or >460 msec (female) within five years before Visit 1.
-
Patients who are treated with glycopyrronium bromide (NVA237) at visit 1 are not allowed to be included into the trialPatients on non-selective beta-blockers. Those patients may enter the study after non-selective beta-blocker withdrawal during a 7-day wash-out period.
-
Patients receiving any other prohibited COPD-related medications specified in Table 5-2 Prohibited COPD related medications must undergo the required wash-out period prior to Visit 2.
-
Patients who are, in the opinion of the investigator known to be unreliable or non-compliant.
-
Patients with a body mass index (BMI) of more than 40 kg/m2.
-
Use of other investigational drugs within 5 half-lives of enrollment or within 30 days, whichever is longer.
-
Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.
-
Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of study treatment.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Novartis Investigative Site | Amstetten | Austria | 3300 | |
| 2 | Novartis Investigative Site | Feldkirch | Austria | 6800 | |
| 3 | Novartis Investigative Site | Hallein | Austria | 5400 | |
| 4 | Novartis Investigative Site | Kirchdorf an der Krems | Austria | 4560 | |
| 5 | Novartis Investigative Site | Leoben | Austria | 8700 | |
| 6 | Novartis Investigative Site | Linz | Austria | 4020 | |
| 7 | Novartis Investigative Site | Perg | Austria | 4320 | |
| 8 | Novartis Investigative Site | Salzburg | Austria | 5020 | |
| 9 | Novartis Investigative Site | Wels | Austria | 4600 | |
| 10 | Novartis Investigative Site | Gosselies | BEL | Belgium | 6041 |
| 11 | Novartis Investigative Site | Gozee | BEL | Belgium | 6534 |
| 12 | Novartis Investigative Site | Zichem | BEL | Belgium | 3271 |
| 13 | Novartis Investigative Site | Antwerpen | Belgium | 2060 | |
| 14 | Novartis Investigative Site | Balen | Belgium | 2490 | |
| 15 | Novartis Investigative Site | Braine l'Alleud | Belgium | 1420 | |
| 16 | Novartis Investigative Site | Brussels | Belgium | 1070 | |
| 17 | Novartis Investigative Site | Bruxelles | Belgium | 1000 | |
| 18 | Novartis Investigative Site | Bruxelles | Belgium | 1200 | |
| 19 | Novartis Investigative Site | Eghezee | Belgium | 5310 | |
| 20 | Novartis Investigative Site | Erpent | Belgium | 5100 | |
| 21 | Novartis Investigative Site | Geraardsbergen | Belgium | 9500 | |
| 22 | Novartis Investigative Site | Gilly | Belgium | 6060 | |
| 23 | Novartis Investigative Site | Halen | Belgium | 3545 | |
| 24 | Novartis Investigative Site | Hasselt | Belgium | 3500 | |
| 25 | Novartis Investigative Site | Heusy | Belgium | 4802 | |
| 26 | Novartis Investigative Site | Ieper | Belgium | 8900 | |
| 27 | Novartis Investigative Site | Knokke-Heist | Belgium | 8300 | |
| 28 | Novartis Investigative Site | Lebbeke | Belgium | 9280 | |
| 29 | Novartis Investigative Site | Liege | Belgium | 4000 | |
| 30 | Novartis Investigative Site | Maaseik | Belgium | 3680 | |
| 31 | Novartis Investigative Site | Malmedy | Belgium | 4960 | |
| 32 | Novartis Investigative Site | Mechelen | Belgium | 2800 | |
| 33 | Novartis Investigative Site | Melsbroek | Belgium | 1820 | |
| 34 | Novartis Investigative Site | Merksem | Belgium | 2170 | |
| 35 | Novartis Investigative Site | Montegnée | Belgium | 4420 | |
| 36 | Novartis Investigative Site | Natoye | Belgium | 5360 | |
| 37 | Novartis Investigative Site | Paal-Beringen | Belgium | 3583 | |
| 38 | Novartis Investigative Site | Ronse | Belgium | 9600 | |
| 39 | Novartis Investigative Site | Saint-Medard | Belgium | 6887 | |
| 40 | Novartis Investigative Site | Seraing | Belgium | 4100 | |
| 41 | Novartis Investigative Site | Tournai | Belgium | 7500 | |
| 42 | Novartis Investigative Site | Verviers | Belgium | 4800 | |
| 43 | Novartis Investigative Site | Vilvoorde | Belgium | 1800 | |
| 44 | Novartis Investigative Site | Zottegem | Belgium | 9620 | |
| 45 | Novartis Investigative Site | Boskovice | Czech Republic | Czechia | 680 01 |
| 46 | Novartis Investigative Site | Brandys Nad Labem | Czech Republic | Czechia | 25001 |
| 47 | Novartis Investigative Site | Brno-Kralovo Pole | Czech Republic | Czechia | 61200 |
| 48 | Novartis Investigative Site | Cvikov | Czech Republic | Czechia | 471 54 |
| 49 | Novartis Investigative Site | Havlickuv Brod | Czech Republic | Czechia | 580 01 |
| 50 | Novartis Investigative Site | Jirkov | Czech Republic | Czechia | 43111 |
| 51 | Novartis Investigative Site | Kurim | Czech Republic | Czechia | 66434 |
| 52 | Novartis Investigative Site | Liberec | Czech Republic | Czechia | 460 01 |
| 53 | Novartis Investigative Site | Lovosice | Czech Republic | Czechia | 410 02 |
| 54 | Novartis Investigative Site | Neratovice | Czech Republic | Czechia | 27711 |
| 55 | Novartis Investigative Site | Ostrava | Czech Republic | Czechia | 708 68 |
| 56 | Novartis Investigative Site | Pardubice | Czech Republic | Czechia | 530 09 |
| 57 | Novartis Investigative Site | Plzen | Czech Republic | Czechia | 33011 |
| 58 | Novartis Investigative Site | Plzen | Czech Republic | Czechia | 331 01 |
| 59 | Novartis Investigative Site | Prague 4 | Czech Republic | Czechia | 142 00 |
| 60 | Novartis Investigative Site | Prague | Czech Republic | Czechia | 130 00 |
| 61 | Novartis Investigative Site | Praha 10 | Czech Republic | Czechia | 108 00 |
| 62 | Novartis Investigative Site | Praha 4 | Czech Republic | Czechia | 140 46 |
| 63 | Novartis Investigative Site | Praha 6 | Czech Republic | Czechia | 163 00 |
| 64 | Novartis Investigative Site | Praha 9 | Czech Republic | Czechia | 19000 |
| 65 | Novartis Investigative Site | Praha | Czech Republic | Czechia | 14800 |
| 66 | Novartis Investigative Site | Rokycany | Czech Republic | Czechia | 337 22 |
| 67 | Novartis Investigative Site | Rudna | Czech Republic | Czechia | 25219 |
| 68 | Novartis Investigative Site | Teplice | Czech Republic | Czechia | 415 01 |
| 69 | Novartis Investigative Site | Trebic | Czech Republic | Czechia | 674 01 |
| 70 | Novartis Investigative Site | Varnsdorf | Czech Republic | Czechia | 40747 |
| 71 | Novartis Investigative Site | Zatec | Czech Republic | Czechia | 438 01 |
| 72 | Novartis Investigative Site | Znojmo | Czech Republic | Czechia | 672 01 |
| 73 | Novartis Investigative Site | Praha 8 | Czechia | 182 00 | |
| 74 | Novartis Investigative Site | Alleroed | Denmark | 3450 | |
| 75 | Novartis Investigative Site | Greve | Denmark | 2670 | |
| 76 | Novartis Investigative Site | Haslev | Denmark | 4690 | |
| 77 | Novartis Investigative Site | Søborg | Denmark | 2860 | |
| 78 | Novartis Investigative Site | Værløse | Denmark | 3500 | |
| 79 | Novartis Investigative Site | Paide | Estonia | 72714 | |
| 80 | Novartis Investigative Site | Tallinn | Estonia | 10138 | |
| 81 | Novartis Investigative Site | Tallinn | Estonia | 10617 | |
| 82 | Novartis Investigative Site | Tallinn | Estonia | 13419 | |
| 83 | Novartis Investigative Site | Tallinn | Estonia | 13619 | |
| 84 | Novartis Investigative Site | Tartu | Estonia | 51014 | |
| 85 | Novartis Investigative Site | Tours Cedex 9 | Indre Et Loire | France | 37044 |
| 86 | Novartis Investigative Site | Briis Sous Forges | France | 91640 | |
| 87 | Novartis Investigative Site | Chamalieres | France | 63400 | |
| 88 | Novartis Investigative Site | Chatellerault | France | 86100 | |
| 89 | Novartis Investigative Site | Forbach | France | 57600 | |
| 90 | Novartis Investigative Site | L'Aigle | France | 61305 | |
| 91 | Novartis Investigative Site | La Bouexiere | France | 35340 | |
| 92 | Novartis Investigative Site | Marseille | France | 13003 | |
| 93 | Novartis Investigative Site | Montpellier | France | 34080 | |
| 94 | Novartis Investigative Site | Murs Erigne | France | 49610 | |
| 95 | Novartis Investigative Site | Nice | France | 06000 | |
| 96 | Novartis Investigative Site | Saint Jean de Luz | France | 64500 | |
| 97 | Novartis Investigative Site | Saint Laurent Du Var | France | 06721 | |
| 98 | Novartis Investigative Site | Saint Pierre | France | 97448 | |
| 99 | Novartis Investigative Site | Strasbourg | France | 67000 | |
| 100 | Novartis Investigative Site | Toulon | France | 83000 | |
| 101 | Novartis Investigative Site | Hannover | Niedersachsen | Germany | 30159 |
| 102 | Novartis Investigative Site | Peine | Niedersachsen | Germany | 31224 |
| 103 | Novartis Investigative Site | Warendorf | Nordrhein-Westfalen | Germany | 48231 |
| 104 | Novartis Investigative Site | Koblenz | NRW | Germany | 56068 |
| 105 | Novartis Investigative Site | Essen | Rheinland Pfalz | Germany | 45127 |
| 106 | Novartis Investigative Site | Cottbus | Sachsen | Germany | 03050 |
| 107 | Novartis Investigative Site | Geesthacht | Schleswig Holstein | Germany | 12502 |
| 108 | Novartis Investigative Site | Annaberg-Buchholz | Germany | 09456 | |
| 109 | Novartis Investigative Site | Auerbach | Germany | 08209 | |
| 110 | Novartis Investigative Site | Augsburg | Germany | 86150 | |
| 111 | Novartis Investigative Site | Bad Neustadt | Germany | 97616 | |
| 112 | Novartis Investigative Site | Bad Salzuflen | Germany | 32105 | |
| 113 | Novartis Investigative Site | Bad Woerishofen | Germany | 86825 | |
| 114 | Novartis Investigative Site | Bamberg | Germany | 96049 | |
| 115 | Novartis Investigative Site | Bensheim | Germany | 64625 | |
| 116 | Novartis Investigative Site | Berlin | Germany | 10117 | |
| 117 | Novartis Investigative Site | Berlin | Germany | 10119 | |
| 118 | Novartis Investigative Site | Berlin | Germany | 10367 | |
| 119 | Novartis Investigative Site | Berlin | Germany | 10625 | |
| 120 | Novartis Investigative Site | Berlin | Germany | 10629 | |
| 121 | Novartis Investigative Site | Berlin | Germany | 10717 | |
| 122 | Novartis Investigative Site | Berlin | Germany | 10787 | |
| 123 | Novartis Investigative Site | Berlin | Germany | 12099 | |
| 124 | Novartis Investigative Site | Berlin | Germany | 12157 | |
| 125 | Novartis Investigative Site | Berlin | Germany | 12159 | |
| 126 | Novartis Investigative Site | Berlin | Germany | 12165 | |
| 127 | Novartis Investigative Site | Berlin | Germany | 12203 | |
| 128 | Novartis Investigative Site | Berlin | Germany | 12627 | |
| 129 | Novartis Investigative Site | Berlin | Germany | 12687 | |
| 130 | Novartis Investigative Site | Berlin | Germany | 13057 | |
| 131 | Novartis Investigative Site | Berlin | Germany | 13086 | |
| 132 | Novartis Investigative Site | Berlin | Germany | 13156 | |
| 133 | Novartis Investigative Site | Berlin | Germany | 13187 | |
| 134 | Novartis Investigative Site | Berlin | Germany | 13507 | |
| 135 | Novartis Investigative Site | Berlin | Germany | 14059 | |
| 136 | Novartis Investigative Site | Berlin | Germany | D-12165 | |
| 137 | Novartis Investigative Site | Bielefeld | Germany | 33617 | |
| 138 | Novartis Investigative Site | Bochum | Germany | 44787 | |
| 139 | Novartis Investigative Site | Bonn | Germany | 53119 | |
| 140 | Novartis Investigative Site | Bonn | Germany | 53123 | |
| 141 | Novartis Investigative Site | Bottrop | Germany | 46240 | |
| 142 | Novartis Investigative Site | Bruchsal | Germany | 76646 | |
| 143 | Novartis Investigative Site | Burgwedel | Germany | 30938 | |
| 144 | Novartis Investigative Site | Daaden | Germany | 57567 | |
| 145 | Novartis Investigative Site | Dachau | Germany | 85221 | |
| 146 | Novartis Investigative Site | Deggendorf | Germany | 94469 | |
| 147 | Novartis Investigative Site | Deggingen | Germany | 73328 | |
| 148 | Novartis Investigative Site | Delitzsch | Germany | 04509 | |
| 149 | Novartis Investigative Site | Dortmund | Germany | 44263 | |
| 150 | Novartis Investigative Site | Dresden | Germany | 01069 | |
| 151 | Novartis Investigative Site | Dresden | Germany | 01129 | |
| 152 | Novartis Investigative Site | Dueren | Germany | 52349 | |
| 153 | Novartis Investigative Site | Dusseldorf | Germany | 40489 | |
| 154 | Novartis Investigative Site | Düsseldorf | Germany | 40211 | |
| 155 | Novartis Investigative Site | Eisenach | Germany | 99817 | |
| 156 | Novartis Investigative Site | Elsterwerda | Germany | 04910 | |
| 157 | Novartis Investigative Site | Erlangen | Germany | 91054 | |
| 158 | Novartis Investigative Site | Essen | Germany | 45138 | |
| 159 | Novartis Investigative Site | Essen | Germany | 45147 | |
| 160 | Novartis Investigative Site | Essen | Germany | 45276 | |
| 161 | Novartis Investigative Site | Essen | Germany | 45277 | |
| 162 | Novartis Investigative Site | Essen | Germany | 45355 | |
| 163 | Novartis Investigative Site | Essen | Germany | 45359 | |
| 164 | Novartis Investigative Site | Foehren | Germany | 54343 | |
| 165 | Novartis Investigative Site | Frankenberg (Eder) | Germany | 35066 | |
| 166 | Novartis Investigative Site | Frankfurt am Main | Germany | 60313 | |
| 167 | Novartis Investigative Site | Frankfurt | Germany | 60389 | |
| 168 | Novartis Investigative Site | Freiburg | Germany | 79104 | |
| 169 | Novartis Investigative Site | Freudenberg | Germany | 57258 | |
| 170 | Novartis Investigative Site | Furstenwalde | Germany | 15517 | |
| 171 | Novartis Investigative Site | Fürstenwalde/Spree | Germany | 15517 | |
| 172 | Novartis Investigative Site | Garmisch-Partenkirchen | Germany | 82467 | |
| 173 | Novartis Investigative Site | Gauting | Germany | 82131 | |
| 174 | Novartis Investigative Site | Gießen | Germany | 35390 | |
| 175 | Novartis Investigative Site | Gifhorn | Germany | 38518 | |
| 176 | Novartis Investigative Site | Goch | Germany | 47574 | |
| 177 | Novartis Investigative Site | Goerlitz | Germany | 02826 | |
| 178 | Novartis Investigative Site | Gummersbach | Germany | 51343 | |
| 179 | Novartis Investigative Site | Gütersloh | Germany | 33330 | |
| 180 | Novartis Investigative Site | Hagen | Germany | 58089 | |
| 181 | Novartis Investigative Site | Halberstadt | Germany | 38820 | |
| 182 | Novartis Investigative Site | Halle | Germany | 06108 | |
| 183 | Novartis Investigative Site | Hamburg | Germany | 20253 | |
| 184 | Novartis Investigative Site | Hamburg | Germany | 20354 | |
| 185 | Novartis Investigative Site | Hamburg | Germany | 20357 | |
| 186 | Novartis Investigative Site | Hamburg | Germany | 22143 | |
| 187 | Novartis Investigative Site | Hamburg | Germany | 22299 | |
| 188 | Novartis Investigative Site | Hamburg | Germany | 22335 | |
| 189 | Novartis Investigative Site | Hamburg | Germany | 22527 | |
| 190 | Novartis Investigative Site | Hannover | Germany | 30163 | |
| 191 | Novartis Investigative Site | Hannover | Germany | 30173 | |
| 192 | Novartis Investigative Site | Hannover | Germany | 30419 | |
| 193 | Novartis Investigative Site | Heidelberg | Germany | 69117 | |
| 194 | Novartis Investigative Site | Hettstedt | Germany | 06333 | |
| 195 | Novartis Investigative Site | Hildesheim | Germany | 31134 | |
| 196 | Novartis Investigative Site | Hoyerswerda | Germany | 02977 | |
| 197 | Novartis Investigative Site | Jena | Germany | 07740 | |
| 198 | Novartis Investigative Site | Jerichow | Germany | 39319 | |
| 199 | Novartis Investigative Site | Kamen | Germany | 59174 | |
| 200 | Novartis Investigative Site | Karlsruhe | Germany | 76199 | |
| 201 | Novartis Investigative Site | Kassel | Germany | 34117 | |
| 202 | Novartis Investigative Site | Kassel | Germany | 34121 | |
| 203 | Novartis Investigative Site | Kiel | Germany | 24105 | |
| 204 | Novartis Investigative Site | Kleve | Germany | 47533 | |
| 205 | Novartis Investigative Site | Koeln | Germany | 50668 | |
| 206 | Novartis Investigative Site | Koeln | Germany | 50937 | |
| 207 | Novartis Investigative Site | Koeln | Germany | 51069 | |
| 208 | Novartis Investigative Site | Koeln | Germany | 51605 | |
| 209 | Novartis Investigative Site | Köthen | Germany | 06366 | |
| 210 | Novartis Investigative Site | Landau-Pfalz | Germany | 76829 | |
| 211 | Novartis Investigative Site | Landsberg | Germany | 86899 | |
| 212 | Novartis Investigative Site | Leipzig | Germany | 04103 | |
| 213 | Novartis Investigative Site | Leipzig | Germany | 04109 | |
| 214 | Novartis Investigative Site | Leipzig | Germany | 04207 | |
| 215 | Novartis Investigative Site | Leipzig | Germany | 04275 | |
| 216 | Novartis Investigative Site | Leipzig | Germany | 04357 | |
| 217 | Novartis Investigative Site | Leonberg | Germany | 71229 | |
| 218 | Novartis Investigative Site | Leverkusen | Germany | 51379 | |
| 219 | Novartis Investigative Site | Limburgerhof | Germany | 67117 | |
| 220 | Novartis Investigative Site | Loehne | Germany | 32584 | |
| 221 | Novartis Investigative Site | Ludwigsburg | Germany | 71640 | |
| 222 | Novartis Investigative Site | Ludwigshafen | Germany | 67061 | |
| 223 | Novartis Investigative Site | Ludwigshafen | Germany | 67067 | |
| 224 | Novartis Investigative Site | Luedenscheid | Germany | 58507 | |
| 225 | Novartis Investigative Site | Lübeck | Germany | 23554 | |
| 226 | Novartis Investigative Site | Magdeburg | Germany | 39112 | |
| 227 | Novartis Investigative Site | Marburg | Germany | 35033 | |
| 228 | Novartis Investigative Site | Marburg | Germany | 35037 | |
| 229 | Novartis Investigative Site | Marburg | Germany | D-35037 | |
| 230 | Novartis Investigative Site | Mayen | Germany | 56727 | |
| 231 | Novartis Investigative Site | Meine | Germany | 38527 | |
| 232 | Novartis Investigative Site | Meissen | Germany | 01662 | |
| 233 | Novartis Investigative Site | Menden | Germany | 58706 | |
| 234 | Novartis Investigative Site | Minden | Germany | 32423 | |
| 235 | Novartis Investigative Site | Mittweida | Germany | 09648 | |
| 236 | Novartis Investigative Site | Mülheim | Germany | 45468 | |
| 237 | Novartis Investigative Site | München | Germany | 80335 | |
| 238 | Novartis Investigative Site | München | Germany | 80802 | |
| 239 | Novartis Investigative Site | Münnerstadt | Germany | 97702 | |
| 240 | Novartis Investigative Site | Neu Isenburg | Germany | 63263 | |
| 241 | Novartis Investigative Site | Neu-Ulm | Germany | 89231 | |
| 242 | Novartis Investigative Site | Neunkirchen | Germany | 66539 | |
| 243 | Novartis Investigative Site | Neuss | Germany | 41462 | |
| 244 | Novartis Investigative Site | Neuwied | Germany | 56564 | |
| 245 | Novartis Investigative Site | Northeim | Germany | 37154 | |
| 246 | Novartis Investigative Site | Nürnberg | Germany | 90443 | |
| 247 | Novartis Investigative Site | Nürnberg | Germany | 90478 | |
| 248 | Novartis Investigative Site | Obermichelbach | Germany | 90587 | |
| 249 | Novartis Investigative Site | Oschatz | Germany | 04758 | |
| 250 | Novartis Investigative Site | Oschersleben | Germany | 39387 | |
| 251 | Novartis Investigative Site | Osnabrueck | Germany | 49074 | |
| 252 | Novartis Investigative Site | Papenburg | Germany | 26871 | |
| 253 | Novartis Investigative Site | Passau | Germany | 94032 | |
| 254 | Novartis Investigative Site | Plauen | Germany | 08523 | |
| 255 | Novartis Investigative Site | Potsdam | Germany | 14467 | |
| 256 | Novartis Investigative Site | Potsdam | Germany | 14469 | |
| 257 | Novartis Investigative Site | Prien A. Chiemsee | Germany | 83209 | |
| 258 | Novartis Investigative Site | Radebeul | Germany | 01445 | |
| 259 | Novartis Investigative Site | Ratingen | Germany | 40878 | |
| 260 | Novartis Investigative Site | Raubach | Germany | 56316 | |
| 261 | Novartis Investigative Site | Reinfeld | Germany | 23858 | |
| 262 | Novartis Investigative Site | Rheine | Germany | 48431 | |
| 263 | Novartis Investigative Site | Rodenbach | Germany | 67688 | |
| 264 | Novartis Investigative Site | Roth | Germany | 91154 | |
| 265 | Novartis Investigative Site | Rudersdorf | Germany | 15562 | |
| 266 | Novartis Investigative Site | Rüsselsheim, | Germany | 65428 | |
| 267 | Novartis Investigative Site | Rüsselsheim | Germany | 65428 | |
| 268 | Novartis Investigative Site | Saalfeld | Germany | 07318 | |
| 269 | Novartis Investigative Site | Saarbruecken | Germany | 66111 | |
| 270 | Novartis Investigative Site | Schleswig | Germany | 24837 | |
| 271 | Novartis Investigative Site | Schwabach | Germany | 91126 | |
| 272 | Novartis Investigative Site | Schwedt | Germany | 16303 | |
| 273 | Novartis Investigative Site | Schwerin | Germany | 19055 | |
| 274 | Novartis Investigative Site | Schwetzingen | Germany | 68723 | |
| 275 | Novartis Investigative Site | Siegen | Germany | 57076 | |
| 276 | Novartis Investigative Site | Sinsheim | Germany | 74889 | |
| 277 | Novartis Investigative Site | Solingen | Germany | 42651 | |
| 278 | Novartis Investigative Site | Solingen | Germany | 42665 | |
| 279 | Novartis Investigative Site | Solingen | Germany | 42697 | |
| 280 | Novartis Investigative Site | Sonneberg | Germany | 96515 | |
| 281 | Novartis Investigative Site | Strausberg | Germany | 15344 | |
| 282 | Novartis Investigative Site | Teuchern | Germany | 06682 | |
| 283 | Novartis Investigative Site | Ulm | Germany | 89073 | |
| 284 | Novartis Investigative Site | Wardenburg | Germany | 26203 | |
| 285 | Novartis Investigative Site | Weilheim | Germany | 82362 | |
| 286 | Novartis Investigative Site | Welzheim | Germany | 73642 | |
| 287 | Novartis Investigative Site | Westerkappeln | Germany | 49492 | |
| 288 | Novartis Investigative Site | Wiesloch | Germany | 69168 | |
| 289 | Novartis Investigative Site | Wissen | Germany | 57537 | |
| 290 | Novartis Investigative Site | Witten | Germany | 58452 | |
| 291 | Novartis Investigative Site | Woellstein | Germany | 55597 | |
| 292 | Novartis Investigative Site | Wolfsburg | Germany | 38448 | |
| 293 | Novartis Investigative Site | Zerbst | Germany | 39261 | |
| 294 | Novartis Investigative Site | Athens | GR | Greece | 115 27 |
| 295 | Novartis Investigative Site | Thessaloniki | GR | Greece | 564 29 |
| 296 | Novartis Investigative Site | Serres | Greece | GR 62 100 | |
| 297 | Novartis Investigative Site | Gyor | HUN | Hungary | 9024 |
| 298 | Novartis Investigative Site | Szazhalombatta | HUN | Hungary | 2440 |
| 299 | Novartis Investigative Site | Cegled | Hungary | 2700 | |
| 300 | Novartis Investigative Site | Debrecen | Hungary | 4026 | |
| 301 | Novartis Investigative Site | Hatvan | Hungary | 3000 | |
| 302 | Novartis Investigative Site | Komarom | Hungary | 2900 | |
| 303 | Novartis Investigative Site | Mako | Hungary | 6900 | |
| 304 | Novartis Investigative Site | Mateszalka | Hungary | 4700 | |
| 305 | Novartis Investigative Site | Pecs | Hungary | 7624 | |
| 306 | Novartis Investigative Site | Pecs | Hungary | 7635 | |
| 307 | Novartis Investigative Site | Szeged | Hungary | 6722 | |
| 308 | Novartis Investigative Site | Tatabanya | Hungary | 2800 | |
| 309 | Novartis Investigative Site | Torokbalint | Hungary | 2045 | |
| 310 | Novartis Investigative Site | County Limerick | Ireland | V94 F858 | |
| 311 | Novartis Investigative Site | Dublin 7 | Ireland | ||
| 312 | Novartis Investigative Site | Dublin | Ireland | 24 | |
| 313 | Novartis Investigative Site | Dublin | Ireland | DUBLIN 8 | |
| 314 | Novartis Investigative Site | Ancona | AN | Italy | 60128 |
| 315 | Novartis Investigative Site | Avellino | AV | Italy | 83100 |
| 316 | Novartis Investigative Site | Bari | BA | Italy | 70123 |
| 317 | Novartis Investigative Site | Bari | BA | Italy | 70124 |
| 318 | Novartis Investigative Site | Terlizzi | BA | Italy | 70038 |
| 319 | Novartis Investigative Site | Triggiano | BA | Italy | 70019 |
| 320 | Novartis Investigative Site | Romano di Lombardia | BG | Italy | 24058 |
| 321 | Novartis Investigative Site | Feltre | BL | Italy | 32032 |
| 322 | Novartis Investigative Site | Telese Terme | BN | Italy | 82037 |
| 323 | Novartis Investigative Site | San Pietro Vernotico | BR | Italy | 72027 |
| 324 | Novartis Investigative Site | Brescia | BS | Italy | 25123 |
| 325 | Novartis Investigative Site | Campobasso | CB | Italy | 86100 |
| 326 | Novartis Investigative Site | Marcianise | CE | Italy | 81025 |
| 327 | Novartis Investigative Site | Caltanissetta | CL | Italy | 93100 |
| 328 | Novartis Investigative Site | Saluzzo | CN | Italy | 12037 |
| 329 | Novartis Investigative Site | Catania | CT | Italy | 95100 |
| 330 | Novartis Investigative Site | Catania | CT | Italy | 95122 |
| 331 | Novartis Investigative Site | Catania | CT | Italy | 95126 |
| 332 | Novartis Investigative Site | Forlì | FC | Italy | 47100 |
| 333 | Novartis Investigative Site | Foggia | FG | Italy | 71100 |
| 334 | Novartis Investigative Site | San Severo | FG | Italy | 71016 |
| 335 | Novartis Investigative Site | Firenze | FI | Italy | 50122 |
| 336 | Novartis Investigative Site | Firenze | FI | Italy | 50134 |
| 337 | Novartis Investigative Site | Genova | GE | Italy | 16100 |
| 338 | Novartis Investigative Site | Livorno | LI | Italy | 57124 |
| 339 | Novartis Investigative Site | Lodi | LO | Italy | 26900 |
| 340 | Novartis Investigative Site | Lido di Camaiore | LU | Italy | 55041 |
| 341 | Novartis Investigative Site | Monza | MB | Italy | 20900 |
| 342 | Novartis Investigative Site | Rozzano | MI | Italy | 20089 |
| 343 | Novartis Investigative Site | Nuoro | NU | Italy | 08100 |
| 344 | Novartis Investigative Site | Palermo | PA | Italy | 90127 |
| 345 | Novartis Investigative Site | Palermo | PA | Italy | 90146 |
| 346 | Novartis Investigative Site | Piacenza | PC | Italy | 29100 |
| 347 | Novartis Investigative Site | Cittadella | PD | Italy | 35013 |
| 348 | Novartis Investigative Site | Pisa | PI | Italy | 56124 |
| 349 | Novartis Investigative Site | Pordenone | PN | Italy | 33170 |
| 350 | Novartis Investigative Site | Voghera | PV | Italy | 27058 |
| 351 | Novartis Investigative Site | Roma | RM | Italy | 00128 |
| 352 | Novartis Investigative Site | Roma | RM | Italy | 00161 |
| 353 | Novartis Investigative Site | Roma | RM | Italy | 00163 |
| 354 | Novartis Investigative Site | Roma | RM | Italy | 00189 |
| 355 | Novartis Investigative Site | Riccione | RN | Italy | 47838 |
| 356 | Novartis Investigative Site | Siena | SI | Italy | 53100 |
| 357 | Novartis Investigative Site | Sondalo | SO | Italy | 23035 |
| 358 | Novartis Investigative Site | Sassari | SS | Italy | 07100 |
| 359 | Novartis Investigative Site | Orbassano | TO | Italy | 10043 |
| 360 | Novartis Investigative Site | Terni | TR | Italy | 05100 |
| 361 | Novartis Investigative Site | Montebelluna | TV | Italy | 31044 |
| 362 | Novartis Investigative Site | Vittorio Veneto | TV | Italy | 31029 |
| 363 | Novartis Investigative Site | Busto Arsizio | VA | Italy | 21052 |
| 364 | Novartis Investigative Site | Arzignano | VI | Italy | 36071 |
| 365 | Novartis Investigative Site | Vicenza | VI | Italy | 36100 |
| 366 | Novartis Investigative Site | Bussolengo | VR | Italy | 37012 |
| 367 | Novartis Investigative Site | Napoli | Italy | 80131 | |
| 368 | Novartis Investigative Site | Torino | Italy | 10149 | |
| 369 | Novartis Investigative Site | Balvi | LVA | Latvia | 4501 |
| 370 | Novartis Investigative Site | Jurmala | LVA | Latvia | LV-2015 |
| 371 | Novartis Investigative Site | Riga | LV | Latvia | 1011 |
| 372 | Novartis Investigative Site | Riga | LV | Latvia | LV-1038 |
| 373 | Novartis Investigative Site | Daugavpils | Latvia | LV-5401 | |
| 374 | Novartis Investigative Site | Riga | Latvia | LV 1002 | |
| 375 | Novartis Investigative Site | Riga | Latvia | LV-1001 | |
| 376 | Novartis Investigative Site | Vilnius | LTU | Lithuania | LT-10207 |
| 377 | Novartis Investigative Site | Kaunas | LT | Lithuania | LT-50128 |
| 378 | Novartis Investigative Site | Vilnius | LT | Lithuania | 01117 |
| 379 | Novartis Investigative Site | Alytus | Lithuania | LT-62114 | |
| 380 | Novartis Investigative Site | Kaunas | Lithuania | 3007 | |
| 381 | Novartis Investigative Site | Klaipeda | Lithuania | LT-92288 | |
| 382 | Novartis Investigative Site | Utena | Lithuania | LT-28151 | |
| 383 | Novartis Investigative Site | Vilnius | Lithuania | 06122 | |
| 384 | Novartis Investigative Site | Vilnius | Lithuania | LT-08661 | |
| 385 | Novartis Investigative Site | Førde | Norway | 6800 | |
| 386 | Novartis Investigative Site | Kløfta | Norway | 2040 | |
| 387 | Novartis Investigative Site | Lierskogen | Norway | 3420 | |
| 388 | Novartis Investigative Site | Oslo | Norway | 0190 | |
| 389 | Novartis Investigative Site | Oslo | Norway | 0953 | |
| 390 | Novartis Investigative Site | Skedsmokorset | Norway | 2020 | |
| 391 | Novartis Investigative Site | Skien | Norway | 3734 | |
| 392 | Novartis Investigative Site | Stavanger | Norway | 4005 | |
| 393 | Novartis Investigative Site | Tananger | Norway | 4056 | |
| 394 | Novartis Investigative Site | Bialystok | Poland | 15-044 | |
| 395 | Novartis Investigative Site | Krakow | Poland | 31-024 | |
| 396 | Novartis Investigative Site | Nowy Dwor Mazowiecki | Poland | 05-100 | |
| 397 | Novartis Investigative Site | Ostrow Wielkopolski | Poland | 63-400 | |
| 398 | Novartis Investigative Site | Pila | Poland | 64-920 | |
| 399 | Novartis Investigative Site | Sopot | Poland | 81-741 | |
| 400 | Novartis Investigative Site | Warszawa | Poland | 01-138 | |
| 401 | Novartis Investigative Site | Wroclaw | Poland | 51-162 | |
| 402 | Novartis Investigative Site | Aveiro | Portugal | 3814-501 | |
| 403 | Novartis Investigative Site | Barcelos | Portugal | 4754-909 | |
| 404 | Novartis Investigative Site | Coimbra | Portugal | 3041-853 | |
| 405 | Novartis Investigative Site | Guimarães | Portugal | 4835-044 | |
| 406 | Novartis Investigative Site | Lisboa | Portugal | 1169-024 | |
| 407 | Novartis Investigative Site | Lisboa | Portugal | 1349-019 | |
| 408 | Novartis Investigative Site | Porto | Portugal | 4200 319 | |
| 409 | Novartis Investigative Site | Vila Franca de Xira | Portugal | 2600-009 | |
| 410 | Novartis Investigative Site | Vila Nova de Gaia | Portugal | 440-230 | |
| 411 | Novartis Investigative Site | Bucharest | District 3 | Romania | 030303 |
| 412 | Novartis Investigative Site | Iasi | Jud. Iasi | Romania | 700115 |
| 413 | Novartis Investigative Site | Bacau | Romania | 600252 | |
| 414 | Novartis Investigative Site | Bragadiru | Romania | 077025 | |
| 415 | Novartis Investigative Site | Constanta | Romania | 900591 | |
| 416 | Novartis Investigative Site | Ramnicu Valcea | Romania | 240564 | |
| 417 | Novartis Investigative Site | Suceava | Romania | 720284 | |
| 418 | Novartis Investigative Site | Timisoara | Romania | 300736 | |
| 419 | Novartis Investigative Site | Chelyabinsk | Russian Federation | 454021 | |
| 420 | Novartis Investigative Site | Kazan | Russian Federation | 420012 | |
| 421 | Novartis Investigative Site | Kemerovo | Russian Federation | 650029 | |
| 422 | Novartis Investigative Site | Moscow | Russian Federation | 101990 | |
| 423 | Novartis Investigative Site | Moscow | Russian Federation | 125315 | |
| 424 | Novartis Investigative Site | N.Novgorod | Russian Federation | 603126 | |
| 425 | Novartis Investigative Site | Novosibirsk | Russian Federation | 630099 | |
| 426 | Novartis Investigative Site | Ryazan | Russian Federation | 390026 | |
| 427 | Novartis Investigative Site | Saint Petersburg | Russian Federation | 197022 | |
| 428 | Novartis Investigative Site | Saratov | Russian Federation | 410012 | |
| 429 | Novartis Investigative Site | Smolensk | Russian Federation | 214019 | |
| 430 | Novartis Investigative Site | St. Petersburg | Russian Federation | 194354 | |
| 431 | Novartis Investigative Site | Tomsk | Russian Federation | 634050 | |
| 432 | Novartis Investigative Site | Ufa | Russian Federation | 450000 | |
| 433 | Novartis Investigative Site | Yaroslavl | Russian Federation | 150003 | |
| 434 | Novartis Investigative Site | Bardejov | Slovak Republic | Slovakia | 085 01 |
| 435 | Novartis Investigative Site | Bojnice | Slovak Republic | Slovakia | 972 01 |
| 436 | Novartis Investigative Site | Liptovsky Hradok | Slovak Republic | Slovakia | 033 01 |
| 437 | Novartis Investigative Site | Námestovo | Slovensko | Slovakia | 02901 |
| 438 | Novartis Investigative Site | Kralovsky Chlmec | Slovakia | 077 01 | |
| 439 | Novartis Investigative Site | Levice | Slovakia | 034 01 | |
| 440 | Novartis Investigative Site | Poprad | Slovakia | 058 01 | |
| 441 | Novartis Investigative Site | Presov | Slovakia | 080 01 | |
| 442 | Novartis Investigative Site | Presov | Slovakia | 08001 | |
| 443 | Novartis Investigative Site | Sala | Slovakia | 927 01 | |
| 444 | Novartis Investigative Site | Sturovo | Slovakia | 943 11 | |
| 445 | Novartis Investigative Site | Trnava | Slovakia | 917 75 | |
| 446 | Novartis Investigative Site | Vrable | Slovakia | 95201 | |
| 447 | Novartis Investigative Site | Golnik | Slovenia | 4204 | |
| 448 | Novartis Investigative Site | Kranj | Slovenia | 4000 | |
| 449 | Novartis Investigative Site | Maribor | Slovenia | 2000 | |
| 450 | Novartis Investigative Site | Murska Sobota | Slovenia | 9000 | |
| 451 | Novartis Investigative Site | Cordoba | Andalucia | Spain | 14004 |
| 452 | Novartis Investigative Site | Marbella | Andalucia | Spain | 29600 |
| 453 | Novartis Investigative Site | Marbella | Andalucia | Spain | 29603 |
| 454 | Novartis Investigative Site | Málaga | Andalucia | Spain | 29010 |
| 455 | Novartis Investigative Site | Badalona | Barcelona | Spain | 08917 |
| 456 | Novartis Investigative Site | Centelles | Barcelona | Spain | 08540 |
| 457 | Novartis Investigative Site | Mataro | Barcelona | Spain | 08303 |
| 458 | Novartis Investigative Site | Sabadell | Barcelona | Spain | 08208 |
| 459 | Novartis Investigative Site | Sant Joan Despi | Barcelona | Spain | 08970 |
| 460 | Novartis Investigative Site | Vic | Barcelona | Spain | 08500 |
| 461 | Novartis Investigative Site | Ponferrada | Castilla Y Leon | Spain | 24400 |
| 462 | Novartis Investigative Site | Salamanca | Castilla Y Leon | Spain | 37007 |
| 463 | Novartis Investigative Site | Barcelona | Cataluna | Spain | 08036 |
| 464 | Novartis Investigative Site | Canet de Mar | Cataluna | Spain | 08360 |
| 465 | Novartis Investigative Site | Sant Boi de Llobregat | Cataluna | Spain | 08830 |
| 466 | Novartis Investigative Site | Badalona | Catalunya | Spain | 08916 |
| 467 | Novartis Investigative Site | Barcelona | Cataluña | Spain | 08035 |
| 468 | Novartis Investigative Site | Vic | Cataluña | Spain | 08500 |
| 469 | Novartis Investigative Site | Alzira | Comunidad Valenciana | Spain | 46600 |
| 470 | Novartis Investigative Site | Benidorm | Comunidad Valenciana | Spain | 03501 |
| 471 | Novartis Investigative Site | Puerto De Sagunto | Comunidad Valenciana | Spain | 46520 |
| 472 | Novartis Investigative Site | Valencia | Comunidad Valenciana | Spain | 46010 |
| 473 | Novartis Investigative Site | Valencia | Comunidad Valenciana | Spain | 46014 |
| 474 | Novartis Investigative Site | Valencia | Comunidad Valenciana | Spain | 46015 |
| 475 | Novartis Investigative Site | Valencia | Comunidad Valenciana | Spain | 46017 |
| 476 | Novartis Investigative Site | Valencia | Comunidad Valenciana | Spain | 46019 |
| 477 | Novartis Investigative Site | Caceres | Extremadura | Spain | 10003 |
| 478 | Novartis Investigative Site | Merida | Extremadura | Spain | 06800 |
| 479 | Novartis Investigative Site | Motril | Granada | Spain | 18600 |
| 480 | Novartis Investigative Site | Mallorca | Islas Baleares | Spain | 07198 |
| 481 | Novartis Investigative Site | Palma de Mallorca | Islas Baleares | Spain | 07014 |
| 482 | Novartis Investigative Site | Madrid | Madrid, Communidad De | Spain | 28022 |
| 483 | Novartis Investigative Site | Mostoles | Madrid, Communidad De | Spain | 28933 |
| 484 | Novartis Investigative Site | Valdemoro | Madrid | Spain | 28342 |
| 485 | Novartis Investigative Site | Madrid | Spain | 28034 | |
| 486 | Novartis Investigative Site | Madrid | Spain | 28040 | |
| 487 | Novartis Investigative Site | Madrid | Spain | 28041 | |
| 488 | Novartis Investigative Site | Santiago de Compostela | Spain | 15706 | |
| 489 | Novartis Investigative Site | Zaragoza | Spain | 50009 | |
| 490 | Novartis Investigative Site | Linkoping | Ostergotlands Lan | Sweden | 587 58 |
| 491 | Novartis Investigative Site | Goteborg | Sweden | 413 46 | |
| 492 | Novartis Investigative Site | Gustavsberg | Sweden | 134 44 | |
| 493 | Novartis Investigative Site | Helsingborg | Sweden | 252 25 | |
| 494 | Novartis Investigative Site | Hollviken | Sweden | 236 32 | |
| 495 | Novartis Investigative Site | Kungshamn | Sweden | 456 31 | |
| 496 | Novartis Investigative Site | Limhamn | Sweden | 216 43 | |
| 497 | Novartis Investigative Site | Lund | Sweden | 222 22 | |
| 498 | Novartis Investigative Site | Råå | Sweden | 252 70 | |
| 499 | Novartis Investigative Site | Umea | Sweden | 907 40 | |
| 500 | Novartis Investigative Site | Vastra Frolunda | Sweden | 421 44 | |
| 501 | Novartis Investigative Site | Aylesbury | Bucks | United Kingdom | HP22 5LB |
| 502 | Novartis Investigative Site | Fowey | Cornwall | United Kingdom | PL23 1DT |
| 503 | Novartis Investigative Site | Liskeard | Cornwall | United Kingdom | PL14 3XA |
| 504 | Novartis Investigative Site | Penzance | Cornwall | United Kingdom | TR18 AJH |
| 505 | Novartis Investigative Site | Redruth | Cornwall | United Kingdom | |
| 506 | Novartis Investigative Site | St Austell | Cornwall | United Kingdom | PL26 7RL |
| 507 | Novartis Investigative Site | Torpoint | Cornwall | United Kingdom | PL11 2TB |
| 508 | Novartis Investigative Site | Bath | England | United Kingdom | BA2 3HT |
| 509 | Novartis Investigative Site | Havant | Hampshire | United Kingdom | PO9 1DQ |
| 510 | Novartis Investigative Site | Burbage | Leicester | United Kingdom | LE10 2SE |
| 511 | Novartis Investigative Site | Daventry | Northamptonshire | United Kingdom | NN11 4DY |
| 512 | Novartis Investigative Site | Sneinton | Nottingham | United Kingdom | NG3 7DQ |
| 513 | Novartis Investigative Site | Axbridge | Somerset | United Kingdom | BS26 2BJ |
| 514 | Novartis Investigative Site | Frome | Somerset | United Kingdom | BA11 2FH |
| 515 | Novartis Investigative Site | Taunton | Somerset | United Kingdom | TA1 5DA |
| 516 | Novartis Investigative Site | South Shields | Tyne And Wear | United Kingdom | NE34 0PL |
| 517 | Novartis Investigative Site | Barry | Vale Of Glamorgan | United Kingdom | CF63 1BA |
| 518 | Novartis Investigative Site | Leamington Spa | Warwickshire | United Kingdom | CV32 4RA |
| 519 | Novartis Investigative Site | Crawley | West Sussex | United Kingdom | RH10 7DX |
| 520 | Novartis Investigative Site | Bradford | West Yorkshire | United Kingdom | BD9 6RJ |
| 521 | Novartis Investigative Site | Trowbridge | Wiltshire | United Kingdom | BA14 8QA |
| 522 | Novartis Investigative Site | Strensall | Yorkshire | United Kingdom | YO32 5UA |
| 523 | Novartis Investigative Site | Bexhill-on-Sea | United Kingdom | TN40 1JJ | |
| 524 | Novartis Investigative Site | Bristol | United Kingdom | BS10 6SP | |
| 525 | Novartis Investigative Site | Bristol | United Kingdom | BS48 1BZ | |
| 526 | Novartis Investigative Site | Cardiff | United Kingdom | CF5 4AD | |
| 527 | Novartis Investigative Site | Chadderton | United Kingdom | OL9 0LH | |
| 528 | Novartis Investigative Site | Cheshire | United Kingdom | CW1 4QJ | |
| 529 | Novartis Investigative Site | Chesterfield | United Kingdom | S40 4AA | |
| 530 | Novartis Investigative Site | Chippenham | United Kingdom | SN14 6GT | |
| 531 | Novartis Investigative Site | Coventry | United Kingdom | CV6 4DD | |
| 532 | Novartis Investigative Site | Hamilton | United Kingdom | ML3 8AA | |
| 533 | Novartis Investigative Site | Lancashire | United Kingdom | FY3 7EN | |
| 534 | Novartis Investigative Site | Manchester | United Kingdom | M8 9JT | |
| 535 | Novartis Investigative Site | Motherwell | United Kingdom | ML1 3JX | |
| 536 | Novartis Investigative Site | Oldham | United Kingdom | OL9 8NH | |
| 537 | Novartis Investigative Site | Plymouth | United Kingdom | PL5 3JB | |
| 538 | Novartis Investigative Site | Shrewsbury | United Kingdom | SY38XQ | |
| 539 | Novartis Investigative Site | South Yorkshire | United Kingdom | DN9 1EP | |
| 540 | Novartis Investigative Site | Stockton on Tees | United Kingdom | TS19 8PE | |
| 541 | Novartis Investigative Site | Vale Of Glanmorgan | United Kingdom | CF63 4AR | |
| 542 | Novartis Investigative Site | Watford | United Kingdom | WD25 7NL | |
| 543 | Novartis Investigative Site | Wiltshire | United Kingdom | SN15 2SB | |
| 544 | Novartis Investigative Site | Wishaw | United Kingdom | ML2 0DP |
Sponsors and Collaborators
- Novartis Pharmaceuticals
Investigators
- Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01985334
Other Study ID Numbers:
- CQVA149A3401
First Posted:
Nov 15, 2013
Last Update Posted:
Mar 19, 2019
Last Verified:
Mar 1, 2019
Keywords provided by Novartis Pharmaceuticals
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | A1 (Any SABA and/or SAMA) | A2 (Glycopyrronium) | B1 (Any LAMA or LABA and mMRC=1) | B2 (Glycopyrronium and mMRC=1) | C1 (Any LABA and ICS) | C2 (Indacaterol/Glycopyrronium) | D1 (Any LAMA or LABA and mMRC>1) | D2 (Indacaterol/Glycopyrronium and mMRC>1) |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Patients treated with any SABA and/or SAMA as monotherapy or in free or fixed dose combination at enrollment and randomized to remain in their baseline therapy with any SABA and/or SAMA | Patients treated with any SABA and/or SAMA as monotherapy or in free or FDC at enrollment and randomized to switch in treatment with glycopyrronium (50 μg o.d.) | Patients treated with any LABA or LAMA monotherapy and mMRC score =1 point at Visit 1 and randomized to remain in their baseline treatment with LABA or LAMA | Patients treated with any LABA or LAMA monotherapy and mMRC score =1 point at Visit 1 and randomized to switch in treatment with glycopyrronium (50 μg o.d.) | Patients treated with any LABA and ICS in free or FDC at enrollment and randomized to remain in their baseline treatment with LABA and ICS in free or FDC | Patients treated with any LABA and ICS in free or FDC at enrollment and randomized to switch in treatment with indacaterol maleate and glycopyrronium bromide FDC (110/50 μg o.d.) | Patients treated with any LABA or LAMA monotherapy and mMRC score >1 point at Visit 1 and randomized to remain their baseline in treatment with LABA or LAMA | Patients treated with any LABA or LAMA monotherapy and mMRC score >1 point at Visit 1 and randomized to switch in treatment with indacaterol maleate and glycopyrronium bromide FDC (110/50 μg o.d.). |
| Period Title: Overall Study | ||||||||
| STARTED | 130 | 387 | 420 | 1262 | 274 | 822 | 274 | 820 |
| The Intention-to-treat (ITT) Population | 122 | 369 | 420 | 1254 | 269 | 811 | 268 | 811 |
| COMPLETED | 107 | 303 | 367 | 1033 | 234 | 666 | 237 | 699 |
| NOT COMPLETED | 23 | 84 | 53 | 229 | 40 | 156 | 37 | 121 |
Baseline Characteristics
| Arm/Group Title | A1 (Any SABA and/or SAMA) | A2 (Glycopyrronium) | B1 (Any LAMA or LABA and mMRC=1) | B2 (Glycopyrronium and mMRC=1) | C1 (Any LABA and ICS) | C2 (Indacaterol/Glycopyrronium) | D1 (Any LAMA or LABA and mMRC>1) | D2 (Indacaterol/Glycopyrronium and mMRC>1) | Total |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Patients treated with any SABA and/or SAMA as monotherapy or in free or fixed dose combination at enrollment and randomized to remain in their baseline therapy with any SABA and/or SAMA | Patients treated with any SABA and/or SAMA as monotherapy or in free or FDC at enrollment and randomized to switch in treatment with glycopyrronium (50 μg o.d.) | Patients treated with any LABA or LAMA monotherapy and mMRC score =1 point at Visit 1 and randomized to remain in their baseline treatment with LABA or LAMA | Patients treated with any LABA or LAMA monotherapy and mMRC score =1 point at Visit 1 and randomized to switch in treatment with glycopyrronium (50 μg o.d.) | Patients treated with any LABA and ICS in free or FDC at enrollment and randomized to remain in their baseline treatment with LABA and ICS in free or FDC | Patients treated with any LABA and ICS in free or FDC at enrollment and randomized to switch in treatment with indacaterol maleate and glycopyrronium bromide FDC (110/50 μg o.d.) | Patients treated with any LABA or LAMA monotherapy and mMRC score >1 point at Visit 1 and randomized to remain their baseline in treatment with LABA or LAMA | Patients treated with any LABA or LAMA monotherapy and mMRC score >1 point at Visit 1 and randomized to switch in treatment with indacaterol maleate and glycopyrronium bromide FDC (110/50 μg o.d.). | Total of all reporting groups |
| Overall Participants | 130 | 387 | 420 | 1262 | 274 | 822 | 274 | 820 | 4389 |
| Age (Years) [Mean (Standard Deviation) ] | |||||||||
| Mean (Standard Deviation) [Years] |
64.2
(8.2)
|
63.2
(8.3)
|
64.6
(8.1)
|
64.4
(8.2)
|
64.4
(9.0)
|
64.7
(8.7)
|
65.1
(7.6)
|
65.4
(8.3)
|
64.6
(8.3)
|
| Sex: Female, Male (Count of Participants) | |||||||||
| Female |
48
36.9%
|
119
30.7%
|
131
31.2%
|
376
29.8%
|
106
38.7%
|
286
34.8%
|
95
34.7%
|
276
33.7%
|
1437
32.7%
|
| Male |
82
63.1%
|
268
69.3%
|
289
68.8%
|
886
70.2%
|
168
61.3%
|
536
65.2%
|
179
65.3%
|
544
66.3%
|
2952
67.3%
|
Outcome Measures
| Title | Trough FEV1 at Week 12 for Group: Glycopyrronium vs. Short-acting Bronchodilators (SABA and/or SAMA as Monotherapy or in Free or FDC) |
|---|---|
| Description | Trough FEV1 at visit 4 is defined as FEV1, computed as the mean of forced expiratory volume in 1 second 15min and 45 min pre dose measurements, at the end of the dosing interval |
| Time Frame | Week 12 (Visit 4) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intention-to-treat (ITT) population consisted of all randomized patients who received at least one dose of the study treatment and who were getting the appropriate medication, be it glycopyrronium, indacaterol + glycopyrronium or comparative treatment (baseline therapy) in the respective comparisons of the different groups |
| Arm/Group Title | A1 (Any SABA and/or SAMA) | A2 (Glycopyrronium) |
|---|---|---|
| Arm/Group Description | Patients treated with any SABA and/or SAMA as monotherapy or in free or fixed dose combination at enrollment and randomized to remain in their baseline therapy with any SABA and/or SAMA | Patients treated with any SABA and/or SAMA as monotherapy or in free or FDC at enrollment and randomized to switch in treatment with glycopyrronium (50 μg o.d.) |
| Measure Participants | 122 | 369 |
| Least Squares Mean (95% Confidence Interval) [Liters] |
1.8264
|
1.8916
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | A1 (Any SABA and/or SAMA), A2 (Glycopyrronium) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0180 |
| Comments | ||
| Method | linear mixed model | |
| Comments | ||
| Title | Trough FEV1 at Week 12 for Group: Glycopyrronium vs. Long-acting Bronchodilators (LABA or LAMA Monotherapy) |
|---|---|
| Description | Trough FEV1 at visit 4 is defined as FEV1, computed as the mean of forced expiratory volume in 1 second 15min and 45 min pre dose measurements, at the end of the dosing interval |
| Time Frame | Week 12 (Visit 4) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intention-to-treat (ITT) population consisted of all randomized patients who received at least one dose of the study treatment and who were getting the appropriate medication, be it glycopyrronium, indacaterol + glycopyrronium or comparative treatment (baseline therapy) in the respective comparisons of the different groups |
| Arm/Group Title | B1 (Any LAMA or LABA and mMRC=1) | B2 (Glycopyrronium and mMRC=1) |
|---|---|---|
| Arm/Group Description | Patients treated with any LABA or LAMA monotherapy and mMRC score =1 point at Visit 1 and randomized to remain in their baseline treatment with LABA or LAMA | Patients treated with any LABA or LAMA monotherapy and mMRC score =1 point at Visit 1 and randomized to switch in treatment with glycopyrronium (50 μg o.d.) |
| Measure Participants | 420 | 1254 |
| Least Squares Mean (95% Confidence Interval) [Liters] |
1.8004
|
1.8215
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | A1 (Any SABA and/or SAMA), A2 (Glycopyrronium) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | H0: Glycopyrronium (50 μg o.d.) [randomized group B2] was inferior to LABA or LAMA (random group B1) with respect to mean trough FEV1 after 12 weeks of treatment. H0: μFEV1, NVA237 - μFEV1, LABA and/or LAMA < -40 mL Ha: Glycopyrronium (50 μg o.d.) [randomized group B2] is non-inferior to LABA or LAMA (random group B1) with respect to mean trough FEV1 after 12 weeks of treatment. Ha: μFEV1, NVA237 - μFEV1, LABA and/or LAMA ≥ -40 mL | |
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | linear mixed model | |
| Comments | ||
| Title | Trough FEV1 at Week 12 for Group: Indacaterol Maleate and Glycopyrronium Bromide FDC vs. LABA and ICS in Free or FDC |
|---|---|
| Description | Trough FEV1 at visit 4 is defined as FEV1, computed as the mean of forced expiratory volume in 1 second 15min and 45 min pre dose measurements, at the end of the dosing interval. |
| Time Frame | Week 12 (Visit 4) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intention-to-treat (ITT) population consisted of all randomized patients who received at least one dose of the study treatment and who were getting the appropriate medication, be it glycopyrronium, indacaterol + glycopyrronium or comparative treatment (baseline therapy) in the respective comparisons of the different groups |
| Arm/Group Title | C1 (Any LABA and ICS) | C2 (Indacaterol/Glycopyrronium) |
|---|---|---|
| Arm/Group Description | Patients treated with any LABA and ICS in free or FDC at enrollment and randomized to remain in their baseline treatment with LABA and ICS in free or FDC | Patients treated with any LABA and ICS in free or FDC at enrollment and randomized to switch in treatment with indacaterol maleate and glycopyrronium bromide FDC (110/50 μg o.d.) |
| Measure Participants | 269 | 811 |
| Least Squares Mean (95% Confidence Interval) [Liters] |
1.6847
|
1.7558
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | A1 (Any SABA and/or SAMA), A2 (Glycopyrronium) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | linear mixed model | |
| Comments | ||
| Title | Trough FEV1 at Week 12 for Group: Indacaterol Maleate and Glycopyrronium Bromide FDC vs. Long-acting Bronchodilators (LABA or LAMA Monotherapy) |
|---|---|
| Description | Trough FEV1 at visit 4 is defined as FEV1, computed as the mean of forced expiratory volume in 1 second 15min and 45 min pre dose measurements, at the end of the dosing interval. |
| Time Frame | Week 12 (Visit 4) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intention-to-treat (ITT) population consisted of all randomized patients who received at least one dose of the study treatment and who were getting the appropriate medication, be it glycopyrronium, indacaterol + glycopyrronium or comparative treatment (baseline therapy) in the respective comparisons of the different groups |
| Arm/Group Title | D1 (Any LAMA or LABA and mMRC>1) | D2 (Indacaterol/Glycopyrronium and mMRC>1) |
|---|---|---|
| Arm/Group Description | Patients treated with any LABA or LAMA monotherapy and mMRC score >1 point at Visit 1 and randomized to remain their baseline in treatment with LABA or LAMA | Patients treated with any LABA or LAMA monotherapy and mMRC score >1 point at Visit 1 and randomized to switch in treatment with indacaterol maleate and glycopyrronium bromide FDC (110/50 μg o.d.). |
| Measure Participants | 268 | 811 |
| Least Squares Mean (95% Confidence Interval) [Liters] |
1.6728
|
1.7742
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | A1 (Any SABA and/or SAMA), A2 (Glycopyrronium) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | linear mixed model | |
| Comments | ||
| Title | Change From Baseline on Transition Dyspnea Index (TDI) for Groups: Glycopyrronium vs. Short-acting Bronchodilators (SABA and/or SAMA as Monotherapy or in Free or FDC) |
|---|---|
| Description | Transition Dyspnea Index (TDI) captures changes from baseline. The TDI score is based on three domains with each domain scored from -3 (major deterioration) to +3 (major improvement), to give an overall score of -9 to +9, a negative score indicating a deterioration from baseline. A TDI focal score of 1 is considered to be a clinically significant improvement from baseline. |
| Time Frame | Day 1 (baseline) and week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intention-to-treat (ITT) population consisted of all randomized patients who received at least one dose of the study treatment and who were getting the appropriate medication, be it glycopyrronium, indacaterol + glycopyrronium or comparative treatment (baseline therapy) in the respective comparisons of the different groups |
| Arm/Group Title | A1 (Any SABA and/or SAMA) | A2 (Glycopyrronium) |
|---|---|---|
| Arm/Group Description | Patients treated with any SABA and/or SAMA as monotherapy or in free or fixed dose combination at enrollment and randomized to remain in their baseline therapy with any SABA and/or SAMA | Patients treated with any SABA and/or SAMA as monotherapy or in free or FDC at enrollment and randomized to switch in treatment with glycopyrronium (50 μg o.d.) |
| Measure Participants | 122 | 369 |
| Least Squares Mean (95% Confidence Interval) [Units on a scale] |
0.5117
|
2.3005
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | A1 (Any SABA and/or SAMA), A2 (Glycopyrronium) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | linear mixed model | |
| Comments | ||
| Title | Change From Baseline on Transition Dyspnea Index (TDI) for Groups: Glycopyrronium vs. Long-acting Bronchodilators (LABA or LAMA Monotherapy) |
|---|---|
| Description | Transition Dyspnea Index (TDI) captures changes from baseline. The TDI score is based on three domains with each domain scored from -3 (major deterioration) to +3 (major improvement), to give an overall score of -9 to +9, a negative score indicating a deterioration from baseline. A TDI focal score of 1 is considered to be a clinically significant improvement from baseline. |
| Time Frame | Day 1 (baseline) and week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intention-to-treat (ITT) population consisted of all randomized patients who received at least one dose of the study treatment and who were getting the appropriate medication, be it glycopyrronium, indacaterol + glycopyrronium or comparative treatment (baseline therapy) in the respective comparisons of the different groups |
| Arm/Group Title | B1 (Any LAMA or LABA and mMRC=1) | B2 (Glycopyrronium and mMRC=1) |
|---|---|---|
| Arm/Group Description | Patients treated with any LABA or LAMA monotherapy and mMRC score =1 point at Visit 1 and randomized to remain in their baseline treatment with LABA or LAMA | Patients treated with any LABA or LAMA monotherapy and mMRC score =1 point at Visit 1 and randomized to switch in treatment with glycopyrronium (50 μg o.d.) |
| Measure Participants | 420 | 1254 |
| Least Squares Mean (95% Confidence Interval) [Units on a scale] |
0.6969
|
1.4351
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | A1 (Any SABA and/or SAMA), A2 (Glycopyrronium) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | A difference of 0.6 points in TDI was adopted as boundary for non-inferiority | |
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | linear mixed model | |
| Comments | ||
| Title | Change From Baseline on Transition Dyspnea Index (TDI) for Groups: Indacaterol Maleate and Glycopyrronium Bromide FDC vs. LABA and ICS in Free or FDC |
|---|---|
| Description | Transition Dyspnea Index (TDI) captures changes from baseline. The TDI score is based on three domains with each domain scored from -3 (major deterioration) to +3 (major improvement), to give an overall score of -9 to +9, a negative score indicating a deterioration from baseline. A TDI focal score of 1 is considered to be a clinically significant improvement from baseline. |
| Time Frame | Day 1 (baseline) and week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intention-to-treat (ITT) population consisted of all randomized patients who received at least one dose of the study treatment and who were getting the appropriate medication, be it glycopyrronium, indacaterol + glycopyrronium or comparative treatment (baseline therapy) in the respective comparisons of the different groups |
| Arm/Group Title | C1 (Any LABA and ICS) | C2 (Indacaterol/Glycopyrronium) |
|---|---|---|
| Arm/Group Description | Patients treated with any LABA and ICS in free or FDC at enrollment and randomized to remain in their baseline treatment with LABA and ICS in free or FDC | Patients treated with any LABA and ICS in free or FDC at enrollment and randomized to switch in treatment with indacaterol maleate and glycopyrronium bromide FDC (110/50 μg o.d.) |
| Measure Participants | 269 | 811 |
| Least Squares Mean (95% Confidence Interval) [Units on a scale] |
0.8508
|
1.9491
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | A1 (Any SABA and/or SAMA), A2 (Glycopyrronium) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | linear mixed model | |
| Comments | ||
| Title | Change From Baseline on Transition Dyspnea Index (TDI) for Groups: Indacaterol Maleate and Glycopyrronium Bromide FDC vs. Long-acting Bronchodilators (LABA or LAMA Monotherapy) |
|---|---|
| Description | Transition Dyspnea Index (TDI) captures changes from baseline. The TDI score is based on three domains with each domain scored from -3 (major deterioration) to +3 (major improvement), to give an overall score of -9 to +9, a negative score indicating a deterioration from baseline. A TDI focal score of 1 is considered to be a clinically significant improvement from baseline. |
| Time Frame | Day 1 (baseline) and week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intention-to-treat (ITT) population consisted of all randomized patients who received at least one dose of the study treatment and who were getting the appropriate medication, be it glycopyrronium, indacaterol + glycopyrronium or comparative treatment (baseline therapy) in the respective comparisons of the different groups |
| Arm/Group Title | D1 (Any LAMA or LABA and mMRC>1) | D2 (Indacaterol/Glycopyrronium and mMRC>1) |
|---|---|---|
| Arm/Group Description | Patients treated with any LABA or LAMA monotherapy and mMRC score >1 point at Visit 1 and randomized to remain their baseline in treatment with LABA or LAMA | Patients treated with any LABA or LAMA monotherapy and mMRC score >1 point at Visit 1 and randomized to switch in treatment with indacaterol maleate and glycopyrronium bromide FDC (110/50 μg o.d.). |
| Measure Participants | 268 | 811 |
| Least Squares Mean (95% Confidence Interval) [Units on a scale] |
0.8632
|
2.1209
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | A1 (Any SABA and/or SAMA), A2 (Glycopyrronium) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | linear mixed model | |
| Comments | ||
| Title | Trough FEV1 at Week 12 for Group: Glycopyrronium vs. Short-acting Bronchodilators (SABA and/or SAMA as Monotherapy or in Free or FDC) or vs. Long-acting Bronchodilators (LABA or LAMA Monotherapy) |
|---|---|
| Description | Trough FEV1 at visit 4 is defined as FEV1, computed as the mean of forced expiratory volume in 1 second 15min and 45 min pre dose measurements, at the end of the dosing interval |
| Time Frame | 12 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intention-to-treat (ITT) population consisted of all randomized patients who received at least one dose of the study treatment and who were getting the appropriate medication, be it glycopyrronium, indacaterol + glycopyrronium or comparative treatment (baseline therapy) in the respective comparisons of the different groups |
| Arm/Group Title | A2 + B2 | A1 + B1 |
|---|---|---|
| Arm/Group Description | A2 (glycopyrronium)+B2 (glycopyrronium and mMRC=1 | A1(any SABA and/or SAMA+B1 (any LAMA or LABA and mMRC=1 |
| Measure Participants | 1623 | 542 |
| Least Squares Mean (95% Confidence Interval) [Liters] |
1.8373
|
1.8065
|
| Title | Change From Baseline on on Transition Dyspnea Index (TDI) for Groups: Glycopyrronium vs. Short-acting Bronchodilators (SABA and/or SAMA as Monotherapy or in Free or FDC) or Long-acting Bronchodilators (LABA or LAMA Monotherapy) |
|---|---|
| Description | Transition Dyspnea Index (TDI) captures changes from baseline. The TDI score is based on three domains with each domain scored from -3 (major deterioration) to +3 (major improvement), to give an overall score of -9 to +9, a negative score indicating a deterioration from baseline. A TDI focal score of 1 is considered to be a clinically significant improvement from baseline. |
| Time Frame | Day 1 (baseline) and week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intention-to-treat (ITT) population consisted of all randomized patients who received at least one dose of the study treatment and who were getting the appropriate medication, be it glycopyrronium, indacaterol + glycopyrronium or comparative treatment (baseline therapy) in the respective comparisons of the different groups |
| Arm/Group Title | A2 +B2 | A1 +B1 |
|---|---|---|
| Arm/Group Description | A2 (glycopyrronium)+B2 (glycopyrronium and mMRC=1 | A1(any SABA and/or SAMA+B1 (any LAMA or LABA and mMRC=1) |
| Measure Participants | 1623 | 542 |
| Least Squares Mean (95% Confidence Interval) [Score on a scale] |
1.6315
|
0.6562
|
| Title | Trough FEV1 at Week 12 for Group: Indacaterol Maleate and Glycopyrronium Bromide FDC vs. LABA or LAMA Monotherapy or LABA and ICS in Free or FDC on Trough FEV1 at Week 12. |
|---|---|
| Description | Trough FEV1 at visit 4 is defined as FEV1, computed as the mean of forced expiratory volume in 1 second 15min and 45 min pre dose measurements, at the end of the dosing interval. |
| Time Frame | 12 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intention-to-treat (ITT) population consisted of all randomized patients who received at least one dose of the study treatment and who were getting the appropriate medication, be it glycopyrronium, indacaterol + glycopyrronium or comparative treatment (baseline therapy) in the respective comparisons of the different groups |
| Arm/Group Title | C2 +D2 | C1 + D1 |
|---|---|---|
| Arm/Group Description | C2 (indacaterol/glycopyrronium)+D2 (indacaterol/glycopyrronium and mMRC>1) | C1 (any LABA and ICS)+D1 (any LAMA or LABA and mMRC>1) |
| Measure Participants | 1622 | 537 |
| Least Squares Mean (95% Confidence Interval) [Liters] |
1.7650
|
1.6789
|
| Title | Change From Baseline on Transition Dyspnea Index (TDI) for Groups: Indacaterol Maleate and Glycopyrronium Bromide FDC vs. LABA or LAMA Monotherapy or LABA and ICS in Free or FDC |
|---|---|
| Description | Transition Dyspnea Index (TDI) captures changes from baseline. The TDI score is based on three domains with each domain scored from -3 (major deterioration) to +3 (major improvement), to give an overall score of -9 to +9, a negative score indicating a deterioration from baseline. A TDI focal score of 1 is considered to be a clinically significant improvement from baseline. |
| Time Frame | Day 1 (baseline) and week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intention-to-treat (ITT) population consisted of all randomized patients who received at least one dose of the study treatment and who were getting the appropriate medication, be it glycopyrronium, indacaterol + glycopyrronium or comparative treatment (baseline therapy) in the respective comparisons of the different groups |
| Arm/Group Title | C2 +D2 | C1 + D1 |
|---|---|---|
| Arm/Group Description | C2 (indacaterol/glycopyrronium) + D2 (indacaterol/glycopyrronium and mMRC>1) | C1 (any LABA and ICS) + D1 (any LAMA or LABA and mMRC>1) |
| Measure Participants | 1622 | 537 |
| Least Squares Mean (95% Confidence Interval) [Score on a scale] |
2.0354
|
0.8588
|
| Title | Change From Baseline on Total Score of COPD Assessment Test (CAT) for Groups: Glycopyrronium and Indacaterol Maleate and Glycopyrronium Bromide FDC |
|---|---|
| Description | Total score of COPD Assessment Test (CAT) will be measured at baseline and at week 12. This questionnaire is completed by the patient. The score ranges from 0-40 where higher scores represent worse health status. CAT scores ≥ 10 are associated with significantly impaired health status. |
| Time Frame | Day 1 (baseline) and Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intention-to-treat (ITT) population consisted of all randomized patients who received at least one dose of the study treatment and who were getting the appropriate medication, be it glycopyrronium, indacaterol + glycopyrronium or comparative treatment (baseline therapy) in the respective comparisons of the different groups |
| Arm/Group Title | A1 (Any SABA and/or SAMA) | A2 (Glycopyrronium) | B1 (Any LAMA or LABA and mMRC=1) | B2 (Glycopyrronium and mMRC=1) | C1 (Any LABA and ICS) | C2 (Indacaterol/Glycopyrronium) | D1 (Any LAMA or LABA and mMRC>1) | D2 (Indacaterol/Glycopyrronium and mMRC>1) |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Patients treated with any SABA and/or SAMA as monotherapy or in free or fixed dose combination at enrollment and randomized to remain in their baseline therapy with any SABA and/or SAMA | Patients treated with any SABA and/or SAMA as monotherapy or in free or FDC at enrollment and randomized to switch in treatment with glycopyrronium (50 μg o.d.) | Patients treated with any LABA or LAMA monotherapy and mMRC score =1 point at Visit 1 and randomized to remain in their baseline treatment with LABA or LAMA | Patients treated with any LABA or LAMA monotherapy and mMRC score =1 point at Visit 1 and randomized to switch in treatment with glycopyrronium (50 μg o.d.) | Patients treated with any LABA and ICS in free or FDC at enrollment and randomized to remain in their baseline treatment with LABA and ICS in free or FDC | Patients treated with any LABA and ICS in free or FDC at enrollment and randomized to switch in treatment with indacaterol maleate and glycopyrronium bromide FDC (110/50 μg o.d.) | Patients treated with any LABA or LAMA monotherapy and mMRC score >1 point at Visit 1 and randomized to remain their baseline in treatment with LABA or LAMA | Patients treated with any LABA or LAMA monotherapy and mMRC score >1 point at Visit 1 and randomized to switch in treatment with indacaterol maleate and glycopyrronium bromide FDC (110/50 μg o.d.). |
| Measure Participants | 122 | 369 | 420 | 1254 | 269 | 811 | 268 | 811 |
| Mean (Standard Deviation) [Score] |
0.1
(4.6)
|
-1.8
(5.3)
|
0.1
(4.9)
|
-0.5
(4.6)
|
-0.4
(4.8)
|
-1.4
(5.4)
|
-0.9
(5.0)
|
-1.9
(5.3)
|
| Title | Change From Baseline on Total Score of Clinical COPD Questionnaire (CCQ) for Groups: Glycopyrronium and Indacaterol Maleate and Glycopyrronium Bromide FDC |
|---|---|
| Description | The Clinical COPD Questionnaire (CCQ) is a self-administered 10-item questionnaire developed to measure clinical control in patients with COPD. Patients will be instructed to recall their experiences during the previous week. They respond to each question using a 7-point scale from 0 = asymptomatic/no imitation to 6 = extremely symptomatic/totally limited. The questionnaire is divided into 3 domains (symptoms [items 1, 2, 5, and 6] functional [items 7, 8, 9, and 10] and mental state [items 3 and 4]). The overall clinical COPD control score and the scores of the domains are calculated by adding all the scores together and dividing this sum by the number of questions. Thus, the overall clinical COPD control score as well as the score on each of the three domains varies between 0 (very good control) to 6 (extremely poor control). |
| Time Frame | Day 1 (baseline) and Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intention-to-treat (ITT) population consisted of all randomized patients who received at least one dose of the study treatment and who were getting the appropriate medication, be it glycopyrronium, indacaterol + glycopyrronium or comparative treatment (baseline therapy) in the respective comparisons of the different groups |
| Arm/Group Title | A1 (Any SABA and/or SAMA) | A2 (Glycopyrronium) | B1 (Any LAMA or LABA and mMRC=1) | B2 (Glycopyrronium and mMRC=1) | C1 (Any LABA and ICS) | C2 (Indacaterol/Glycopyrronium) | D1 (Any LAMA or LABA and mMRC>1) | D2 (Indacaterol/Glycopyrronium and mMRC>1) |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Patients treated with any SABA and/or SAMA as monotherapy or in free or fixed dose combination at enrollment and randomized to remain in their baseline therapy with any SABA and/or SAMA | Patients treated with any SABA and/or SAMA as monotherapy or in free or FDC at enrollment and randomized to switch in treatment with glycopyrronium (50 μg o.d.) | Patients treated with any LABA or LAMA monotherapy and mMRC score =1 point at Visit 1 and randomized to remain in their baseline treatment with LABA or LAMA | Patients treated with any LABA or LAMA monotherapy and mMRC score =1 point at Visit 1 and randomized to switch in treatment with glycopyrronium (50 μg o.d.) | Patients treated with any LABA and ICS in free or FDC at enrollment and randomized to remain in their baseline treatment with LABA and ICS in free or FDC | Patients treated with any LABA and ICS in free or FDC at enrollment and randomized to switch in treatment with indacaterol maleate and glycopyrronium bromide FDC (110/50 μg o.d.) | Patients treated with any LABA or LAMA monotherapy and mMRC score >1 point at Visit 1 and randomized to remain their baseline in treatment with LABA or LAMA | Patients treated with any LABA or LAMA monotherapy and mMRC score >1 point at Visit 1 and randomized to switch in treatment with indacaterol maleate and glycopyrronium bromide FDC (110/50 μg o.d.). |
| Measure Participants | 122 | 369 | 420 | 1254 | 269 | 811 | 268 | 811 |
| Mean (Standard Deviation) [Score] |
-0.0
(0.6)
|
-0.3
(0.7)
|
0.0
(0.7)
|
-0.1
(0.7)
|
-0.1
(0.7)
|
-0.2
(0.8)
|
-0.1
(0.8)
|
-0.3
(0.8)
|
| Title | Mean Number of Puffs of Rescue Medication Use for Groups: Glycopyrronium and Indacaterol Maleate and Glycopyrronium Bromide FDC |
|---|---|
| Description | Mean number of puffs of rescue medication use will be measured using eDiary data over 12 weeks of treatment. |
| Time Frame | 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intention-to-treat (ITT) population consisted of all randomized patients who received at least one dose of the study treatment and who were getting the appropriate medication, be it glycopyrronium, indacaterol + glycopyrronium or comparative treatment (baseline therapy) in the respective comparisons of the different groups |
| Arm/Group Title | A1 (Any SABA and/or SAMA) | A2 (Glycopyrronium) | B1 (Any LAMA or LABA and mMRC=1) | B2 (Glycopyrronium and mMRC=1) | C1 (Any LABA and ICS) | C2 (Indacaterol/Glycopyrronium) | D1 (Any LAMA or LABA and mMRC>1) | D2 (Indacaterol/Glycopyrronium and mMRC>1) |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Patients treated with any SABA and/or SAMA as monotherapy or in free or fixed dose combination at enrollment and randomized to remain in their baseline therapy with any SABA and/or SAMA | Patients treated with any SABA and/or SAMA as monotherapy or in free or FDC at enrollment and randomized to switch in treatment with glycopyrronium (50 μg o.d.) | Patients treated with any LABA or LAMA monotherapy and mMRC score =1 point at Visit 1 and randomized to remain in their baseline treatment with LABA or LAMA | Patients treated with any LABA or LAMA monotherapy and mMRC score =1 point at Visit 1 and randomized to switch in treatment with glycopyrronium (50 μg o.d.) | Patients treated with any LABA and ICS in free or FDC at enrollment and randomized to remain in their baseline treatment with LABA and ICS in free or FDC | Patients treated with any LABA and ICS in free or FDC at enrollment and randomized to switch in treatment with indacaterol maleate and glycopyrronium bromide FDC (110/50 μg o.d.) | Patients treated with any LABA or LAMA monotherapy and mMRC score >1 point at Visit 1 and randomized to remain their baseline in treatment with LABA or LAMA | Patients treated with any LABA or LAMA monotherapy and mMRC score >1 point at Visit 1 and randomized to switch in treatment with indacaterol maleate and glycopyrronium bromide FDC (110/50 μg o.d.). |
| Measure Participants | 122 | 369 | 420 | 1254 | 269 | 811 | 268 | 811 |
| Mean (Standard Deviation) [Number of puffs] |
1.8
(1.7)
|
1.0
(1.3)
|
0.8
(1.2)
|
0.7
(1.1)
|
1.6
(1.7)
|
1.1
(1.4)
|
1.4
(1.4)
|
1.1
(1.3)
|
| Title | Mean Change From Baseline Reported Symptoms of COPD for Groups: Glycopyrronium and Indacaterol Maleate and Glycopyrronium Bromide FDC |
|---|---|
| Description | Patient-reported symptoms of COPD combined will be measured using eDiary data reported over the 12 week treatment period. The mean total symptom scores and mean individual symptom scores for the patient were calculated for the whole study period. The mean change from baseline in the total scores and in the individual scores were summarized by treatment and were analyzed for the percentage of nights with no nighttime awakenings and percentage of days with no symptoms. |
| Time Frame | Baseline, 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intention-to-treat (ITT) population consisted of all randomized patients who received at least one dose of the study treatment and who were getting the appropriate medication, be it glycopyrronium, indacaterol + glycopyrronium or comparative treatment (baseline therapy) in the respective comparisons of the different groups |
| Arm/Group Title | A1 (Any SABA and/or SAMA) | A2 (Glycopyrronium) | B1 (Any LAMA or LABA and mMRC=1) | B2 (Glycopyrronium and mMRC=1) | C1 (Any LABA and ICS) | C2 (Indacaterol/Glycopyrronium) | D1 (Any LAMA or LABA and mMRC>1) | D2 (Indacaterol/Glycopyrronium and mMRC>1) |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Patients treated with any SABA and/or SAMA as monotherapy or in free or fixed dose combination at enrollment and randomized to remain in their baseline therapy with any SABA and/or SAMA | Patients treated with any SABA and/or SAMA as monotherapy or in free or FDC at enrollment and randomized to switch in treatment with glycopyrronium (50 μg o.d.) | Patients treated with any LABA or LAMA monotherapy and mMRC score =1 point at Visit 1 and randomized to remain in their baseline treatment with LABA or LAMA | Patients treated with any LABA or LAMA monotherapy and mMRC score =1 point at Visit 1 and randomized to switch in treatment with glycopyrronium (50 μg o.d.) | Patients treated with any LABA and ICS in free or FDC at enrollment and randomized to remain in their baseline treatment with LABA and ICS in free or FDC | Patients treated with any LABA and ICS in free or FDC at enrollment and randomized to switch in treatment with indacaterol maleate and glycopyrronium bromide FDC (110/50 μg o.d.) | Patients treated with any LABA or LAMA monotherapy and mMRC score >1 point at Visit 1 and randomized to remain their baseline in treatment with LABA or LAMA | Patients treated with any LABA or LAMA monotherapy and mMRC score >1 point at Visit 1 and randomized to switch in treatment with indacaterol maleate and glycopyrronium bromide FDC (110/50 μg o.d.). |
| Measure Participants | 122 | 369 | 420 | 1254 | 269 | 811 | 268 | 811 |
| Mean (Standard Deviation) [Percentage of days] |
-0.04
(0.15)
|
-0.10
(0.22)
|
-0.03
(0.19)
|
-0.05
(0.20)
|
-0.05
(0.19)
|
-0.07
(0.22)
|
-0.04
(0.19)
|
-0.09
(0.21)
|
Adverse Events
| Time Frame | ||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||||||||||
| Arm/Group Title | A1 (Any SABA and/or SAMA) | A2 (Glycopyrronium) | B1 (Any LAMA or@ LABA and mMRC eq 1) | B2 (Glycopyrronium@ and mMRC eq 1) | C1 (Any LABA and ICS) | C2 (Indacaterol/@Glycopyrronium) | D1 (Any LAMA or@ LABA and mMRC gt 1) | D2 (Indacaterol/@Glycopyrronium and@ mMRC gt 1) | ||||||||
| Arm/Group Description | Patients treated with any SABA and/or SAMA as monotherapy or in free or fixed dose combination at enrollment and randomized to remain in their baseline therapy with any SABA and/or SAMA | Patients treated with any SABA and/or SAMA as monotherapy or in free or FDC at enrollment and randomized to switch in treatment with glycopyrronium (50 μg o.d.) | Patients treated with any LABA or LAMA monotherapy and mMRC score =1 point at Visit 1 and randomized to remain in their baseline treatment with LABA or LAMA | Patients treated with any LABA or LAMA monotherapy and mMRC score =1 point at Visit 1 and randomized to switch in treatment with glycopyrronium (50 μg o.d.) | Patients treated with any LABA and ICS in free or FDC at enrollment and randomized to remain in their baseline treatment with LABA and ICS in free or FDC | Patients treated with any LABA and ICS in free or FDC at enrollment and randomized to switch in treatment with indacaterol maleate and glycopyrronium bromide FDC (110/50 μg o.d.) | Patients treated with any LABA or LAMA monotherapy and mMRC score >1 point at Visit 1 and randomized to remain their baseline in treatment with LABA or LAMA | Patients treated with any LABA or LAMA monotherapy and mMRC score >1 point at Visit 1 and randomized to switch in treatment with indacaterol maleate and glycopyrronium bromide FDC (110/50 μg o.d.). | ||||||||
All Cause Mortality |
||||||||||||||||
| A1 (Any SABA and/or SAMA) | A2 (Glycopyrronium) | B1 (Any LAMA or@ LABA and mMRC eq 1) | B2 (Glycopyrronium@ and mMRC eq 1) | C1 (Any LABA and ICS) | C2 (Indacaterol/@Glycopyrronium) | D1 (Any LAMA or@ LABA and mMRC gt 1) | D2 (Indacaterol/@Glycopyrronium and@ mMRC gt 1) | |||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||||||
Serious Adverse Events |
||||||||||||||||
| A1 (Any SABA and/or SAMA) | A2 (Glycopyrronium) | B1 (Any LAMA or@ LABA and mMRC eq 1) | B2 (Glycopyrronium@ and mMRC eq 1) | C1 (Any LABA and ICS) | C2 (Indacaterol/@Glycopyrronium) | D1 (Any LAMA or@ LABA and mMRC gt 1) | D2 (Indacaterol/@Glycopyrronium and@ mMRC gt 1) | |||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 4/125 (3.2%) | 9/385 (2.3%) | 11/417 (2.6%) | 30/1248 (2.4%) | 6/269 (2.2%) | 22/816 (2.7%) | 10/269 (3.7%) | 34/814 (4.2%) | ||||||||
| Blood and lymphatic system disorders | ||||||||||||||||
| Anaemia | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 1/1248 (0.1%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Immune thrombocytopenic purpura | 0/125 (0%) | 1/385 (0.3%) | 0/417 (0%) | 0/1248 (0%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Cardiac disorders | ||||||||||||||||
| Acute coronary syndrome | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 1/1248 (0.1%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Acute myocardial infarction | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 2/1248 (0.2%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 1/814 (0.1%) | ||||||||
| Angina pectoris | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 0/1248 (0%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 1/814 (0.1%) | ||||||||
| Angina unstable | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 0/1248 (0%) | 0/269 (0%) | 0/816 (0%) | 1/269 (0.4%) | 0/814 (0%) | ||||||||
| Aortic valve incompetence | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 1/1248 (0.1%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Aortic valve stenosis | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 1/1248 (0.1%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Arrhythmia | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 1/1248 (0.1%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Arteriosclerosis coronary artery | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 0/1248 (0%) | 1/269 (0.4%) | 0/816 (0%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Atrial fibrillation | 0/125 (0%) | 1/385 (0.3%) | 0/417 (0%) | 1/1248 (0.1%) | 0/269 (0%) | 1/816 (0.1%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Cardiac arrest | 1/125 (0.8%) | 0/385 (0%) | 0/417 (0%) | 0/1248 (0%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Cardiac failure | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 1/1248 (0.1%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 1/814 (0.1%) | ||||||||
| Coronary artery disease | 0/125 (0%) | 2/385 (0.5%) | 1/417 (0.2%) | 0/1248 (0%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Ischaemic cardiomyopathy | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 1/1248 (0.1%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Left ventricular failure | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 0/1248 (0%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 1/814 (0.1%) | ||||||||
| Myocardial infarction | 1/125 (0.8%) | 0/385 (0%) | 0/417 (0%) | 1/1248 (0.1%) | 0/269 (0%) | 0/816 (0%) | 1/269 (0.4%) | 1/814 (0.1%) | ||||||||
| Myocardial ischaemia | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 1/1248 (0.1%) | 0/269 (0%) | 0/816 (0%) | 1/269 (0.4%) | 0/814 (0%) | ||||||||
| Supraventricular tachycardia | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 0/1248 (0%) | 0/269 (0%) | 1/816 (0.1%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Tachycardia | 0/125 (0%) | 1/385 (0.3%) | 0/417 (0%) | 0/1248 (0%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Congenital, familial and genetic disorders | ||||||||||||||||
| Congenital central nervous system anomaly | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 0/1248 (0%) | 0/269 (0%) | 1/816 (0.1%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Hydrocele | 1/125 (0.8%) | 0/385 (0%) | 0/417 (0%) | 0/1248 (0%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Ear and labyrinth disorders | ||||||||||||||||
| Vertigo | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 0/1248 (0%) | 0/269 (0%) | 2/816 (0.2%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Gastrointestinal disorders | ||||||||||||||||
| Abdominal hernia | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 1/1248 (0.1%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Abdominal incarcerated hernia | 0/125 (0%) | 1/385 (0.3%) | 0/417 (0%) | 0/1248 (0%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Constipation | 0/125 (0%) | 0/385 (0%) | 1/417 (0.2%) | 0/1248 (0%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Diverticulum oesophageal | 0/125 (0%) | 1/385 (0.3%) | 0/417 (0%) | 0/1248 (0%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Faecaloma | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 1/1248 (0.1%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Gastrointestinal haemorrhage | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 1/1248 (0.1%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Inguinal hernia | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 1/1248 (0.1%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Pancreatitis | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 1/1248 (0.1%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| General disorders | ||||||||||||||||
| Chest pain | 0/125 (0%) | 1/385 (0.3%) | 0/417 (0%) | 2/1248 (0.2%) | 0/269 (0%) | 1/816 (0.1%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Fatigue | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 0/1248 (0%) | 0/269 (0%) | 1/816 (0.1%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Hernia | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 0/1248 (0%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 1/814 (0.1%) | ||||||||
| Sudden death | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 0/1248 (0%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 1/814 (0.1%) | ||||||||
| Ulcer | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 0/1248 (0%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 1/814 (0.1%) | ||||||||
| Hepatobiliary disorders | ||||||||||||||||
| Bile duct stone | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 0/1248 (0%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 1/814 (0.1%) | ||||||||
| Biliary tract disorder | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 1/1248 (0.1%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Hepatic cirrhosis | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 0/1248 (0%) | 0/269 (0%) | 1/816 (0.1%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Immune system disorders | ||||||||||||||||
| Anaphylactic shock | 0/125 (0%) | 0/385 (0%) | 1/417 (0.2%) | 0/1248 (0%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Drug hypersensitivity | 0/125 (0%) | 1/385 (0.3%) | 0/417 (0%) | 0/1248 (0%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Infections and infestations | ||||||||||||||||
| Bronchitis | 0/125 (0%) | 0/385 (0%) | 1/417 (0.2%) | 0/1248 (0%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 1/814 (0.1%) | ||||||||
| Cystitis | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 0/1248 (0%) | 1/269 (0.4%) | 0/816 (0%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Diverticulitis | 0/125 (0%) | 0/385 (0%) | 1/417 (0.2%) | 0/1248 (0%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Influenza | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 0/1248 (0%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 1/814 (0.1%) | ||||||||
| Mediastinal abscess | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 0/1248 (0%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 1/814 (0.1%) | ||||||||
| Oesophageal candidiasis | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 0/1248 (0%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 1/814 (0.1%) | ||||||||
| Pneumonia | 0/125 (0%) | 1/385 (0.3%) | 0/417 (0%) | 2/1248 (0.2%) | 0/269 (0%) | 1/816 (0.1%) | 1/269 (0.4%) | 7/814 (0.9%) | ||||||||
| Injury, poisoning and procedural complications | ||||||||||||||||
| Ankle fracture | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 0/1248 (0%) | 0/269 (0%) | 1/816 (0.1%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Bursa injury | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 0/1248 (0%) | 0/269 (0%) | 1/816 (0.1%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Facial bones fracture | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 1/1248 (0.1%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Femoral neck fracture | 0/125 (0%) | 0/385 (0%) | 1/417 (0.2%) | 0/1248 (0%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Femur fracture | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 0/1248 (0%) | 0/269 (0%) | 1/816 (0.1%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Fracture | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 0/1248 (0%) | 0/269 (0%) | 0/816 (0%) | 1/269 (0.4%) | 0/814 (0%) | ||||||||
| Hip fracture | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 0/1248 (0%) | 0/269 (0%) | 1/816 (0.1%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Jaw fracture | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 0/1248 (0%) | 0/269 (0%) | 0/816 (0%) | 1/269 (0.4%) | 0/814 (0%) | ||||||||
| Ligament rupture | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 0/1248 (0%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 1/814 (0.1%) | ||||||||
| Rib fracture | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 0/1248 (0%) | 0/269 (0%) | 0/816 (0%) | 1/269 (0.4%) | 1/814 (0.1%) | ||||||||
| Splenic rupture | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 0/1248 (0%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 1/814 (0.1%) | ||||||||
| Traumatic intracranial haemorrhage | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 0/1248 (0%) | 0/269 (0%) | 0/816 (0%) | 1/269 (0.4%) | 0/814 (0%) | ||||||||
| Wound dehiscence | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 0/1248 (0%) | 0/269 (0%) | 1/816 (0.1%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Investigations | ||||||||||||||||
| Blood pressure increased | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 0/1248 (0%) | 0/269 (0%) | 1/816 (0.1%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Heart rate decreased | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 1/1248 (0.1%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Metabolism and nutrition disorders | ||||||||||||||||
| Dehydration | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 0/1248 (0%) | 1/269 (0.4%) | 0/816 (0%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||||
| Back pain | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 1/1248 (0.1%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Osteoarthritis | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 1/1248 (0.1%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Pseudarthrosis | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 1/1248 (0.1%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Synovitis | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 0/1248 (0%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 1/814 (0.1%) | ||||||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||
| Bladder neoplasm | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 1/1248 (0.1%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Brain neoplasm | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 1/1248 (0.1%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Breast cancer | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 0/1248 (0%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 2/814 (0.2%) | ||||||||
| Bronchial carcinoma | 0/125 (0%) | 1/385 (0.3%) | 0/417 (0%) | 1/1248 (0.1%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 1/814 (0.1%) | ||||||||
| Colon cancer | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 0/1248 (0%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 1/814 (0.1%) | ||||||||
| Laryngeal cancer | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 1/1248 (0.1%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Lung adenocarcinoma | 1/125 (0.8%) | 0/385 (0%) | 0/417 (0%) | 1/1248 (0.1%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Metastases to bone | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 1/1248 (0.1%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Oropharyngeal cancer | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 0/1248 (0%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 1/814 (0.1%) | ||||||||
| Prostate cancer | 0/125 (0%) | 0/385 (0%) | 1/417 (0.2%) | 0/1248 (0%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Squamous cell carcinoma of the tongue | 0/125 (0%) | 0/385 (0%) | 1/417 (0.2%) | 0/1248 (0%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Nervous system disorders | ||||||||||||||||
| Cerebral ischaemia | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 1/1248 (0.1%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Cerebrovascular accident | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 1/1248 (0.1%) | 0/269 (0%) | 1/816 (0.1%) | 1/269 (0.4%) | 0/814 (0%) | ||||||||
| Cerebrovascular disorder | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 0/1248 (0%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 1/814 (0.1%) | ||||||||
| Cerebrovascular insufficiency | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 1/1248 (0.1%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Embolic cerebral infarction | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 1/1248 (0.1%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Loss of consciousness | 0/125 (0%) | 0/385 (0%) | 1/417 (0.2%) | 0/1248 (0%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Ruptured cerebral aneurysm | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 0/1248 (0%) | 0/269 (0%) | 0/816 (0%) | 1/269 (0.4%) | 0/814 (0%) | ||||||||
| Syncope | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 0/1248 (0%) | 0/269 (0%) | 1/816 (0.1%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Transient ischaemic attack | 1/125 (0.8%) | 0/385 (0%) | 0/417 (0%) | 0/1248 (0%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Vascular dementia | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 0/1248 (0%) | 1/269 (0.4%) | 0/816 (0%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Vascular encephalopathy | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 0/1248 (0%) | 1/269 (0.4%) | 0/816 (0%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Psychiatric disorders | ||||||||||||||||
| Alcoholism | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 1/1248 (0.1%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Depression | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 0/1248 (0%) | 1/269 (0.4%) | 0/816 (0%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Renal and urinary disorders | ||||||||||||||||
| Nephrolithiasis | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 0/1248 (0%) | 0/269 (0%) | 1/816 (0.1%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||
| Chronic obstructive pulmonary disease | 0/125 (0%) | 1/385 (0.3%) | 1/417 (0.2%) | 3/1248 (0.2%) | 1/269 (0.4%) | 3/816 (0.4%) | 1/269 (0.4%) | 3/814 (0.4%) | ||||||||
| Pneumothorax | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 0/1248 (0%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 1/814 (0.1%) | ||||||||
| Pulmonary embolism | 0/125 (0%) | 0/385 (0%) | 1/417 (0.2%) | 0/1248 (0%) | 0/269 (0%) | 0/816 (0%) | 1/269 (0.4%) | 1/814 (0.1%) | ||||||||
| Pulmonary haemorrhage | 1/125 (0.8%) | 0/385 (0%) | 0/417 (0%) | 0/1248 (0%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Pulmonary oedema | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 1/1248 (0.1%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Respiratory depression | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 0/1248 (0%) | 0/269 (0%) | 1/816 (0.1%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Skin and subcutaneous tissue disorders | ||||||||||||||||
| Blister | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 0/1248 (0%) | 0/269 (0%) | 1/816 (0.1%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Vascular disorders | ||||||||||||||||
| Aortic aneurysm | 0/125 (0%) | 1/385 (0.3%) | 0/417 (0%) | 0/1248 (0%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Aortic stenosis | 0/125 (0%) | 1/385 (0.3%) | 0/417 (0%) | 0/1248 (0%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Circulatory collapse | 0/125 (0%) | 0/385 (0%) | 1/417 (0.2%) | 0/1248 (0%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Deep vein thrombosis | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 0/1248 (0%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 2/814 (0.2%) | ||||||||
| Femoral artery aneurysm | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 0/1248 (0%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 1/814 (0.1%) | ||||||||
| Hypertension | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 0/1248 (0%) | 0/269 (0%) | 1/816 (0.1%) | 1/269 (0.4%) | 1/814 (0.1%) | ||||||||
| Hypertensive crisis | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 0/1248 (0%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 1/814 (0.1%) | ||||||||
| Intermittent claudication | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 0/1248 (0%) | 0/269 (0%) | 0/816 (0%) | 1/269 (0.4%) | 0/814 (0%) | ||||||||
| Ischaemia | 0/125 (0%) | 1/385 (0.3%) | 0/417 (0%) | 0/1248 (0%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Peripheral arterial occlusive disease | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 0/1248 (0%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 3/814 (0.4%) | ||||||||
| Peripheral artery aneurysm | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 0/1248 (0%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 1/814 (0.1%) | ||||||||
| Peripheral artery stenosis | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 0/1248 (0%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 3/814 (0.4%) | ||||||||
| Peripheral artery thrombosis | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 0/1248 (0%) | 1/269 (0.4%) | 0/816 (0%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Shock | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 1/1248 (0.1%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 0/814 (0%) | ||||||||
| Thrombophlebitis superficial | 0/125 (0%) | 0/385 (0%) | 0/417 (0%) | 0/1248 (0%) | 0/269 (0%) | 0/816 (0%) | 0/269 (0%) | 1/814 (0.1%) | ||||||||
Other (Not Including Serious) Adverse Events |
||||||||||||||||
| A1 (Any SABA and/or SAMA) | A2 (Glycopyrronium) | B1 (Any LAMA or@ LABA and mMRC eq 1) | B2 (Glycopyrronium@ and mMRC eq 1) | C1 (Any LABA and ICS) | C2 (Indacaterol/@Glycopyrronium) | D1 (Any LAMA or@ LABA and mMRC gt 1) | D2 (Indacaterol/@Glycopyrronium and@ mMRC gt 1) | |||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 19/125 (15.2%) | 67/385 (17.4%) | 63/417 (15.1%) | 163/1248 (13.1%) | 29/269 (10.8%) | 119/816 (14.6%) | 20/269 (7.4%) | 120/814 (14.7%) | ||||||||
| Gastrointestinal disorders | ||||||||||||||||
| Dyspepsia | 2/125 (1.6%) | 0/385 (0%) | 1/417 (0.2%) | 3/1248 (0.2%) | 0/269 (0%) | 2/816 (0.2%) | 0/269 (0%) | 1/814 (0.1%) | ||||||||
| Infections and infestations | ||||||||||||||||
| Bronchitis | 0/125 (0%) | 4/385 (1%) | 4/417 (1%) | 4/1248 (0.3%) | 1/269 (0.4%) | 1/816 (0.1%) | 1/269 (0.4%) | 3/814 (0.4%) | ||||||||
| Nasopharyngitis | 8/125 (6.4%) | 38/385 (9.9%) | 24/417 (5.8%) | 71/1248 (5.7%) | 11/269 (4.1%) | 37/816 (4.5%) | 10/269 (3.7%) | 54/814 (6.6%) | ||||||||
| Pharyngitis | 3/125 (2.4%) | 1/385 (0.3%) | 0/417 (0%) | 7/1248 (0.6%) | 0/269 (0%) | 3/816 (0.4%) | 1/269 (0.4%) | 5/814 (0.6%) | ||||||||
| Rhinitis | 0/125 (0%) | 1/385 (0.3%) | 7/417 (1.7%) | 12/1248 (1%) | 2/269 (0.7%) | 5/816 (0.6%) | 1/269 (0.4%) | 10/814 (1.2%) | ||||||||
| Tracheitis | 2/125 (1.6%) | 0/385 (0%) | 2/417 (0.5%) | 2/1248 (0.2%) | 0/269 (0%) | 2/816 (0.2%) | 0/269 (0%) | 2/814 (0.2%) | ||||||||
| Urinary tract infection | 2/125 (1.6%) | 2/385 (0.5%) | 1/417 (0.2%) | 5/1248 (0.4%) | 0/269 (0%) | 1/816 (0.1%) | 0/269 (0%) | 3/814 (0.4%) | ||||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||||
| Back pain | 2/125 (1.6%) | 6/385 (1.6%) | 3/417 (0.7%) | 8/1248 (0.6%) | 2/269 (0.7%) | 10/816 (1.2%) | 2/269 (0.7%) | 11/814 (1.4%) | ||||||||
| Nervous system disorders | ||||||||||||||||
| Headache | 0/125 (0%) | 7/385 (1.8%) | 3/417 (0.7%) | 9/1248 (0.7%) | 1/269 (0.4%) | 12/816 (1.5%) | 1/269 (0.4%) | 8/814 (1%) | ||||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||
| Cough | 3/125 (2.4%) | 5/385 (1.3%) | 13/417 (3.1%) | 33/1248 (2.6%) | 5/269 (1.9%) | 44/816 (5.4%) | 4/269 (1.5%) | 27/814 (3.3%) | ||||||||
| Dyspnoea | 1/125 (0.8%) | 5/385 (1.3%) | 6/417 (1.4%) | 13/1248 (1%) | 6/269 (2.2%) | 7/816 (0.9%) | 2/269 (0.7%) | 7/814 (0.9%) | ||||||||
| Oropharyngeal pain | 0/125 (0%) | 4/385 (1%) | 3/417 (0.7%) | 10/1248 (0.8%) | 4/269 (1.5%) | 3/816 (0.4%) | 1/269 (0.4%) | 4/814 (0.5%) | ||||||||
| Productive cough | 0/125 (0%) | 4/385 (1%) | 0/417 (0%) | 1/1248 (0.1%) | 0/269 (0%) | 2/816 (0.2%) | 2/269 (0.7%) | 0/814 (0%) | ||||||||
| Vascular disorders | ||||||||||||||||
| Hypertension | 1/125 (0.8%) | 3/385 (0.8%) | 7/417 (1.7%) | 7/1248 (0.6%) | 2/269 (0.7%) | 5/816 (0.6%) | 0/269 (0%) | 7/814 (0.9%) | ||||||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Novartis Pharmaceuticals |
| Phone | 862-778-8300 |
Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01985334
Other Study ID Numbers:
- CQVA149A3401
First Posted:
Nov 15, 2013
Last Update Posted:
Mar 19, 2019
Last Verified:
Mar 1, 2019